Polarizing versus depolarizing blood cardioplegia: An experimental study of myocardial function, metabolism and ultrastructure following cardiopulmonary bypass and cardioplegic arrest

In cardiothoracic surgery, the use of the heart-lung machine for cardiopulmonary bypass (CPB) and induced cardiac arrest, cardioplegia, is required for performing the majority of the surgical procedures. Myocardial protection is essential during the ischemic period of cardioplegia. The aim of this project is to evaluate and verify if a recently developed routine for myocardial protection is feasible, safe and suited for use in clinical practice. This pre-clinical translational animal research project is designed to bridge the gap between basic research and new routines that may benefit the patient. In three different protocols, two groups of animals (10 in each group) are randomized to polarized or depolarized cardioplegic arrest. The novel and unexplored cardioplegic solution with esmolol, adenosine and magnesium; St Thomas’ Hospital polarizing cardioplegia (STH-POL) is compared with today’s gold standard; potassium-based St Thomas’ depolarizing solution (STH-2), both administered as repeated, cold, oxygenated blood. Left ventricular regional and global function in the early hours after weaning from CPB are evaluated together with myocardial ultrastructure and metabolism. Our hypothesis is that STH-POL improves myocardial protection demonstrated as better preserved postoperative cardiac function in a large animal translational model. This knowledge is essential before initiating clinical studies and implementation. An optimal myocardial protection is important when performing cardiac surgery in an ageing population with increased occurrence of more complex heart diseases and comorbidity. Paper I demonstrated improved regional and global contractility following 60 min of cardioplegic arrest with STH-POL compared to STH-2 blood cardioplegia. After weaning from CPB and following reperfusion, left ventricular dP/dtmax, Preload Recruitable Stroke Work and radial peak systolic strain rate were maintained 180 min after declamping in the group with polarized arrest and decreased with depolarized arrest. Paper II focused on energy metabolism and ultrastructure with the STH-POL compared to the STH-2 cardioplegia during 60 min of cardiac arrest and at early reperfusion. The study demonstrated increased levels of creatine phosphate in left ventricular myocardial tissue samples at the end of the period of cardioplegic arrest and early after reperfusion in the STH-POL compared to the STH-2 group. Furthermore, the adenosine triphosphate content was increased and the mitochondrial surface-to-volume ratio decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion. However, at 180 min after reperfusion these group differences were negligible. Paper III addressed myocardial function after prolonged cardioplegic arrest for 120 min. A temporary increase in the load-independent contractility variable Preload Recruitable Stroke Work was seen in the STH-POL compared to the STH-2 group 150 min after declamping. Neither regional nor global left ventricular function differed between groups up to 240 min after declamping. However, compared to the STH-2 group, the left ventricular myocardial tissue blood flow rate decreased in the STHPOL group at 150 and 240 min compared to 60 min after declamping. The relationship between the left ventricular total pressure-volume area and blood flow rate was maintained after declamping in the STH-POL group and decreased in the STH-2 group. Thus, cardioplegic arrest with STH-POL alleviated the mismatch between myocardial function and perfusion after weaning from CPB compared to STH-2. Conclusion: In a porcine model, cardioplegic arrest with St. Thomas´ Hospital polarizing solution offered comparable myocardial protection and improved myocardial function (Paper I), preserved energy status (Paper II) and enhanced contractile efficiency (Paper III) in the early hours after weaning from cardiopulmonary bypass compared to St. Thomas´ Hospital No 2 blood cardioplegia

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model

OBJECTIVES: This study investigated whether the novel St. Thomas’ Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers improved myocardial protection by reducing demands for high-energy phosphates during cardiac arrest compared to the depolarizing St. Thomas’ Hospital cardioplegic solution No 2 (STH-2). METHODS: Twenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, repeated, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were continuously recorded. Left ventricular biopsies, snap-frozen in liquid nitrogen or fixed in glutaraldehyde, were obtained at Baseline, 58 min after cross-clamp and 20 and 180 min after weaning from bypass. Adenine nucleotides were evaluated by high-performance liquid chromatography, myocardial ultrastructure with morphometry. RESULTS: With STH-POL myocardial creatine phosphate was increased compared to STH-2 at 58 min of cross-clamp [59.9 ± 6.4 (SEM) vs 44.5 ± 7.4 nmol/mg protein; P < 0.025], and at 20 min after reperfusion (61.0 ± 6.7 vs 49.0 ± 5.5 nmol/mg protein; P < 0.05), ATP levels were increased at 20 min of reperfusion with STH-POL (35.4 ± 1.1 vs 32.4 ± 1.2 nmol/mg protein; P < 0.05). Mitochondrial surface-to-volume ratio was decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion (6.74 ± 0.14 vs 7.46 ± 0.13 µm2/µm3; P = 0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion and onwards, cardiac index was increased with STH-POL; 4.8 ± 0.2 compared to 4.0 ± 0.2 l/min/m2 (P = 0.011) for STH-2 at 180 min. CONCLUSIONS: Polarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.publishedVersio

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model

Introduction: This experimental study compares myocardial function after prolonged arrest by St. Thomas’ Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas’ Hospital No 2, both administered as cold oxygenated blood cardioplegia. Methods: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. Results: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). Conclusion: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.publishedVersio

Polarizing versus depolarizing blood cardioplegia: An experimental study of myocardial function, metabolism and ultrastructure following cardiopulmonary bypass and cardioplegic arrest

In cardiothoracic surgery, the use of the heart-lung machine for cardiopulmonary bypass (CPB) and induced cardiac arrest, cardioplegia, is required for performing the majority of the surgical procedures. Myocardial protection is essential during the ischemic period of cardioplegia. The aim of this project is to evaluate and verify if a recently developed routine for myocardial protection is feasible, safe and suited for use in clinical practice. This pre-clinical translational animal research project is designed to bridge the gap between basic research and new routines that may benefit the patient. In three different protocols, two groups of animals (10 in each group) are randomized to polarized or depolarized cardioplegic arrest. The novel and unexplored cardioplegic solution with esmolol, adenosine and magnesium; St Thomas’ Hospital polarizing cardioplegia (STH-POL) is compared with today’s gold standard; potassium-based St Thomas’ depolarizing solution (STH-2), both administered as repeated, cold, oxygenated blood. Left ventricular regional and global function in the early hours after weaning from CPB are evaluated together with myocardial ultrastructure and metabolism. Our hypothesis is that STH-POL improves myocardial protection demonstrated as better preserved postoperative cardiac function in a large animal translational model. This knowledge is essential before initiating clinical studies and implementation. An optimal myocardial protection is important when performing cardiac surgery in an ageing population with increased occurrence of more complex heart diseases and comorbidity. Paper I demonstrated improved regional and global contractility following 60 min of cardioplegic arrest with STH-POL compared to STH-2 blood cardioplegia. After weaning from CPB and following reperfusion, left ventricular dP/dtmax, Preload Recruitable Stroke Work and radial peak systolic strain rate were maintained 180 min after declamping in the group with polarized arrest and decreased with depolarized arrest. Paper II focused on energy metabolism and ultrastructure with the STH-POL compared to the STH-2 cardioplegia during 60 min of cardiac arrest and at early reperfusion. The study demonstrated increased levels of creatine phosphate in left ventricular myocardial tissue samples at the end of the period of cardioplegic arrest and early after reperfusion in the STH-POL compared to the STH-2 group. Furthermore, the adenosine triphosphate content was increased and the mitochondrial surface-to-volume ratio decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion. However, at 180 min after reperfusion these group differences were negligible. Paper III addressed myocardial function after prolonged cardioplegic arrest for 120 min. A temporary increase in the load-independent contractility variable Preload Recruitable Stroke Work was seen in the STH-POL compared to the STH-2 group 150 min after declamping. Neither regional nor global left ventricular function differed between groups up to 240 min after declamping. However, compared to the STH-2 group, the left ventricular myocardial tissue blood flow rate decreased in the STHPOL group at 150 and 240 min compared to 60 min after declamping. The relationship between the left ventricular total pressure-volume area and blood flow rate was maintained after declamping in the STH-POL group and decreased in the STH-2 group. Thus, cardioplegic arrest with STH-POL alleviated the mismatch between myocardial function and perfusion after weaning from CPB compared to STH-2. Conclusion: In a porcine model, cardioplegic arrest with St. Thomas´ Hospital polarizing solution offered comparable myocardial protection and improved myocardial function (Paper I), preserved energy status (Paper II) and enhanced contractile efficiency (Paper III) in the early hours after weaning from cardiopulmonary bypass compared to St. Thomas´ Hospital No 2 blood cardioplegia

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model

OBJECTIVES: This study investigated whether the novel St. Thomas’ Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers improved myocardial protection by reducing demands for high-energy phosphates during cardiac arrest compared to the depolarizing St. Thomas’ Hospital cardioplegic solution No 2 (STH-2). METHODS: Twenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, repeated, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were continuously recorded. Left ventricular biopsies, snap-frozen in liquid nitrogen or fixed in glutaraldehyde, were obtained at Baseline, 58 min after cross-clamp and 20 and 180 min after weaning from bypass. Adenine nucleotides were evaluated by high-performance liquid chromatography, myocardial ultrastructure with morphometry. RESULTS: With STH-POL myocardial creatine phosphate was increased compared to STH-2 at 58 min of cross-clamp [59.9 ± 6.4 (SEM) vs 44.5 ± 7.4 nmol/mg protein; P < 0.025], and at 20 min after reperfusion (61.0 ± 6.7 vs 49.0 ± 5.5 nmol/mg protein; P < 0.05), ATP levels were increased at 20 min of reperfusion with STH-POL (35.4 ± 1.1 vs 32.4 ± 1.2 nmol/mg protein; P < 0.05). Mitochondrial surface-to-volume ratio was decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion (6.74 ± 0.14 vs 7.46 ± 0.13 µm2/µm3; P = 0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion and onwards, cardiac index was increased with STH-POL; 4.8 ± 0.2 compared to 4.0 ± 0.2 l/min/m2 (P = 0.011) for STH-2 at 180 min. CONCLUSIONS: Polarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion

Fiskebiologiske undersøkelser i Limingen, Nord-Trøndelag, 2016

Sandlund, O.T., Brabrand, Å., Davidsen, J.G., Gjelland, K.Ø., Heggberget, T.G., Knudsen, R., Pettersen, O., Saksgård, L., Sjursen, A. og Aass, P. 2017. Fiskebiologiske undersøkelser i Limingen, Nord-Trøndelag, 2016. - NINA Rapport 1334. 37 s. Fiskesamfunnet i Limingen omfatter røye, aure, ørekyt og trepigget stingsild. Også kanadarøye fanges fra tid til annen. Røyebestanden inkluderer tre økologiske former: normalrøye, dvergrøye og grårøye. Selv om bestanden av normalrøye trolig har gått mye tilbake siden reguleringene (6 m i 1953 og ytterligere 2,7 m i 1963) finnes det fremdeles en livskraftig bestand. Det samme gjelder dvergrøye og grårøye som trolig har vært mindre berørt av reguleringene. Aurebestanden i innsjøen har hatt en minst like kraftig tilbakegang som normalrøya, og har i dag dårlig vekst og lav kondisjonsfaktor. Dette skyldes både begrensete gyte- og oppvekstmuligheter og en vid og utvasket strandssone. Basert på fiskebestanden må økologisk tilstand for Limingen settes til «dårlig», og det er ingen realistiske tiltak som kan bringe bestanden opp til «god» tilstand. Dette passer med at Limingens tilstand i Vann-nett er satt til sterkt modifisert vannforekomst (SMVF). Det ble prøvefisket med både bunnsatte og pelagiske nordisk oversiktgarn og pelagisk trål i august-september 2016. Målt som fangst per innsats (antall fisk per 100 m2 garnareal per natt, CPUE) dominerte ørekyt og aure i strandsona (CPUE lik hhv. 7,5 og 3,1). Fra 10 m til mer enn 50 m dyp dominerte røye i fangstene. Fangsten av normalrøye var størst i 20-30 m dyp (CPUE=5,0), mens CPUE for både dvergrøye og grårøye var størst i 30-50 m dyp (CPUE hhv. 7,8 og 2,2). I de åpne vannmassene ble det bare fanget normalrøye. I flytegarna ble det fanget kun ni normalrøye mellom 14 og 40 cm, mens trålfangsten bestod av 63 normalrøye mellom 4 og 30 cm. Normalrøya hadde best vekst av røyeformene, og stagnerte i vekst ved ca. 35 cm ved seks-sju års alder. Dette er også alder ved kjønnsmodning. Dvergrøya vokste langsomt og nådde ca. 23 cm ved 10 års alder. Grårøyas vekst var en mellomting mellom disse, og den nådde ca. 25 cm ved åtte års alder. Aurens vekst var dårlig, ca. 3,7 cm i året fram til sju års alder, da gjennomsnittlig lengde var ca. 26 cm. Aure fra Gjersvika, der vannstanden holdes stabil ved hjelp av en terskel, hadde vekstomslag ved 4-5 års alder og nådde 43,5 cm ved sju år. Kondisjonsfaktoren til både normalrøye og aure over 25 cm var 0,86. Ca. 45 % av normalrøya over 15 cm hadde rød kjøttfarge, mens bare 29 % av auren hadde rødt kjøtt. Dietten til normalrøya var dominert av dyreplankton og mysis, med et mindre innslag av overflateinsekter, bunndyr og fisk. Hos dvergrøya var mysis viktigste næringsdyr sammen med dyreplankton, mens grårøya tok mest fisk og mysis. Hos auren var overflateinsekter og dyreplankton de viktigste næringsdyra. Mysis utgjorde bare en liten andel av mageinnholdet til auren, og fisk ble bare så vidt registrert. Både røye (normalrøye) og aure har gått kraftig tilbake i Limingen etter reguleringene. For røyas del er dette i noen grad kompensert ved at fiskens vekst og kvalitet er relativt god. Dette skyldes sannsynligvis det «nye» næringsdyret mysis som ble introdusert tidlig på 1970-tallet. Den fåtallige aurebestanden har langsom vekst og lav kondisjonsfaktor, og ser ikke ut til å utnytte den introduserte ørekyta som byttedyr. I Gjersvika, der vannstanden holdes stabil vha. en terskel, viser auren vekstomslag som tyder på at den har langt bedre næringsforhold enn i selve Limingen, og muligens i noen grad utnytter ørekyt som byttefisk. Utfisking av ørekyt med teiner kan gi store fangster med relativt liten arbeidsinnsats på habitater med stor tetthet, f.eks. på terskelen mellom Limingen og Gjersvika. Tiltak for å bedre aurebestanden i Limingen vil eventuelt være å sikre best mulig adgang til de begrensete gytearealene som finnes i tilløpsbekker. Dette kan omfatte både å holde vannstanden så høy i gytetida at fisken får lett adgang til bekkene, og fysiske tiltak i reguleringssona som sikrer oppvandringsmulighet og som hindrer at rogn gytes på områder som senere blir tørrlagt. En viktig begrensning for auren er likevel liten tilgang på næring i den regulerte strandsona, slik at en kraftig økning av aurebestanden ikke vil finne gode vekstforhold. Utsetting av fisk er derfor ikke et aktuelt tiltak. For røyas del er spesielle tiltak ikke nødvendige.Sandlund, O.T., Brabrand, Å., Davidsen, J.G., Gjelland, K.Ø., Heggberget, T.G., Knudsen, R., Pettersen, O., Saksgård, L., Sjursen, A. and Aass, P. 2017. Survey of the fish stock in Lake Lim-ingen, Nord-Trøndelag, 2016. - NINA Report 1334. 37 s. The fish community in Lake Limingen includes Arctic charr (Salvelinus alpinus), brown trout (Salmo trutta), European minnow (Phoxinus phoxinus) and three-spined stickleback (Gasteros-teus aculeatus). Lake trout (Salvelinus namaycush) has occasionally been recorded in the lake. Only Arctic charr and brown trout are native to the lake. The population of Arctic charr consists of three ecomorphs: “normal charr”, “dwarf charr” and “grey charr”. Although the population of normal charr has declined by 70-80% since the hydropower regulation of the lake in 1953 and 1961 (total regulation amplitude: 8.7 m), there is still a vital population of this ecomorph in the lake. This is also the case for the deep-water dwarf and grey charr, both of which probably have-been less affected by the hydropower regulation. The population of brown trout experienced a similar decline since 1953, and presently exists in a relatively sparse population with poor growth. Brown trout suffers from poor spawning and recruitment opportunities, and an eroded littoral zone with lean feeding conditions. Based on the documented decline in the population abundance of normal charr and brown trout, the ecological status of the fish community in Lake Limingen is classified as “poor”, which is in line with the classification of the lake as “heavily modified water body” (HMWB) (cf. www.vann-nett.no). Survey fishing was performed in August-September 2016 with benthic and pelagic Nordic survey nets as well as a pelagic pair trawl. CPUE (number of fish per 100 m2 net area per night) was dominated by minnow and brown trout in the littoral zone (CPUE = 7.5 and 3.1, respectively). Between 10 m and more than 50 m depth, CPUE was dominated by Arctic charr. Maximum catch of normal charr (CPUE = 5.0) was at 20-30 m depth, while both dwarf and grey charr were most numerous at 30-50 m depth (CPUE = 7.8 and 2.2, respectively). The pelagic gill net and trawl catches contained only normal charr (gill net CPUE = 0.6). In pelagic gill nets, the fish varied between 14 and 40 cm in body length, while the pair trawl catches contained fish between 4 and 30 cm in length. Normal charr had the highest growth rate of the charr ecomorphs, reaching approx. 35 cm at 6-7 years. Dwarf charr had the slowest growth rate, reaching 23 cm at 10 years, while grey charr had intermediate growth, reaching 25 cm at 8 years. Brown trout grew poorly, at an annual rate of 3.7 cm, stagnating at around 27 cm at age 7. In Gjersvika bay, which is a part of the lake where water level is kept relatively stable by a sill at the bay entrance, brown trout showed a shift in growth rate at an age of 4-5 years, reaching 43.5 cm at age 7. The body condition (Fulton’s K) of normal charr and brown trout larger than 25 cm was 0.86. Approx. 45% of normal charr larger than 15 cm had red flesh, while only 29% of similarly sized brown trout had red flesh. The stomach contents of normal charr was dominated by the introduced Mysis relicta and crustacean zooplankton, with small amounts of surface insects, zoobenthos and fish. Dwarf charr had eaten M. relicta and zooplankton, while grey charr had eaten M. relicta and fish. Brown trout had mainly taken surface insects and zooplankton, and very small amounts of M. relicta. Fish was barely recorded in trout stomachs. The decline in normal charr since the 1950s has to a limited extent been compensated by improved growth and quality, likely due to the introduced prey species M. relicta. The sparse brown trout population exhibits slow growth rates and low condition factor, and appears not to be able to utilize the introduced potential prey fish, European minnow. The recruitment to the brown trout population has been severely reduced when both the inflowing and outflowing rivers were regulated, barring access to major spawning areas. Possible measures to improve the brown trout stock in Lake Limingen should focus on ensuring access to the limited spawning and recruitment areas that still do exist in small inflowing streams. This may include managing the water level during spawning migration as well as habitat measures in the regulation zone to prevent spawning in areas that will be left dry during winter. However, with the eroded littoral zone, there will be limited food available for the trout population, and stocking with trout should not be prioritized. The normal charr population does not require any new management measures

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model

Introduction: This experimental study compares myocardial function after prolonged arrest by St. Thomas’ Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas’ Hospital No 2, both administered as cold oxygenated blood cardioplegia. Methods: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. Results: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). Conclusion: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB

Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass

OBJECTIVES Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure–conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0.008). Radial peak ejection strain rate increased and the load-independent variable preload recruitable stroke work was increased with polarizing cardioplegia after 180 min, 64 ± 3 vs 54 ± 2 mmHg (P = 0.018), indicating better preserved left ventricular contractility with polarizing cardioplegia. Phosphorylation of GRK2 in myocardial tissue did not differ between groups. Fractional cytoplasmic volume in myocytes was reduced in hearts arrested with polarizing cardioplegia, indicating reduction of cytoplasmic oedema. CONCLUSIONS Polarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia