Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB

Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway

<p>Abstract</p> <p>Background</p> <p>To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).</p> <p>Methods</p> <p>Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.</p> <p>Results</p> <p>Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.</p> <p>Conclusions</p> <p>After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.</p

Central and mixed venous blood oxygen correlate well during acute normovolemic hemodilution in anesthetized pigs

BACKGROUND: Central venous oxygen saturation (ScvO2) and oxygen tension (PcvO2), obtained from the superior vena cava, correlate well with mixed venous (pulmonary arterial) oxygen saturation (SvO2) and tension (pvO2) when the hematocrit is normal. The present study was undertaken to assess whether extreme hemodilution affects this relation. METHODS: We compared mixed and central venous blood during graded arterial desaturation (inspired fraction of oxygen (FIO2) between 1.0 and 0.10) in 10 hemodiluted pigs, and in 10 pigs with normal hematocrit (control), during fentanyl-ketamine-pancuronium anesthesia and mechanical ventilation. RESULTS: Arterial oxygen saturation decreased from 100% at FIO2 = 1.0 to 44 +/- 12% at FIO2 = 0.10 (mean +/- SD). Venous oxygen saturation ranged from 3.5% to 97.3%. The regression coefficient between SvO2 and ScvO2 was 0.97 (R2 = 0.93, bias -2.4 +/- 5.8%) in the hemodiluted and 0.99 (R2 = 0.97, bias -3.0 +/- 5.0%) in the control group. Venous oxygen tension values ranged from 0.5 kPa to 9.5 kPa, and the regression coefficient for oxygen tension was 0.94 (R2 = 0.89, bias -0.20 +/- 0.47 kPa) in the hemodiluted and 0.99 (R2 = 0.97, bias -0.43 +/- 0.48 kPa) in the control group. The regression coefficient for pH was 0.95 in the hemodiluted and 0.98 in the control animals. CONCLUSION: The findings indicate that also during hemodilution monitoring of central venous blood oxygen may be as useful as monitoring of mixed venous blood oxygen

Nitrous oxide reduces inspired oxygen fraction but does not compromise circulation and oxygenation during hemodilution in pigs

BACKGROUND: The use of nitrous oxide (N2O) during hemodilution has been questioned. Nitrous oxide reduces the inspired oxygen fraction (F1O2), depresses myocardial function and may reduce cardiac output (CO) and systemic oxygen delivery (DO2SY). The aim of this study was to evaluate the importance of the effects of nitrous oxide on systemic and myocardial circulation and oxygenation during extreme, acute, normovolemic hemodilution. METHODS: Ten midazolam-fentanyl-pancuronium anesthetized pigs were exposed to 65% N2O before and after extreme isovolemic hemodilution (hematocrit 33 +/- 1% and 10 +/- 1%, respectively). Systemic and myocardial hemodynamics, oxygen delivery and consumption and blood lactate were measured before (at F1O2 1.0 and 0.35) and during N2O exposure. RESULTS: Hemodilution caused an increase in CO from 137 +/- 43 to 229 +/- 32 ml.kg-1.min-1 (P < 0.01), a decrease in systemic vascular resistance (from 42 +/- 14 to 20 +/- 4 mmHg.L-1.min-1, P < 0.05), a decrease in mean arterial blood pressure (from 119 +/- 19 to 100 +/- 26 mmHg, P < 0.05) and a decrease in DO2SY from 21.1 +/- 6.9 to 13.7 +/- 2.1 ml.kg-1.min-1 (P < 0.01). Cardiac venous blood flow increased by 135% (P < 0.01) and cardiac venous saturation from 25 +/- 6 to 41 +/- 5% (P < 0.05). After hemodilution, changing F1O2 from 1.0 to 0.35 reduced arterial blood oxygen content from 59.4 +/- 3.7 to 52.3 +/- 5.1 ml.L-1 (P < 0.01), mixed venous saturation (SvO2) from 75 +/- 9 to 47 +/- 7% (P < 0.05) and DO2SY from 13.7 +/- 2.1 to 11.9 +/- 2.3 ml.kg-1.min-1 (P < 0.05). Dissolved oxygen at F1O2 = 1.0 and F1O2 = 0.35 constituted 25.4 +/- 3.1% and 10.1 +/- 1.5%, respectively, of systemic oxygen delivery after hemodilution, compared with 10.7 +/- 1.2% and 3.9 +/- 0.5% before hemodilution (P < 0.01). Left ventricular oxygen delivery and consumption were unchanged. Exposure to N2O did not affect mean arterial blood pressure or systemic vascular resistance before or after hemodilution. After hemodilution during N2O-exposure, CO and DO2SY decreased by 9% (P < 0.01 and P < 0.05, respectively), but no changes in SvO2, systemic oxygen uptake or arterial lactate were observed. The effect of N2O on myocardial oxygenation was similar before and after hemodilution; cardiac venous blood flow, left ventricular oxygen delivery and uptake decreased, but no animals showed left ventricular lactate production. CONCLUSION: Nitrous oxide did not compromise systemic and myocardial circulation and oxygenation during acute normovolemic hemodilution in pigs. Possible adverse effects from the use of nitrous oxide during hemodilution seem to be related to a reduced F1O2, reducing the safety margin for systemic oxygen delivery

Inotropic Support During Experimental Endotoxemic Shock: Part II. A Comparison of Levosimendan with Dobutamine

BACKGROUND: We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock. METHODS: Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO2) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 mu g . kg(-1) . h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 mu g . kg(-1) . h(-1)), dobutamine (10-20 mu g . kg(-1) . min(-1)), and control. In the first two groups, norepinephrine (0.5-2 mu g . kg(-1) . min(-1)) was added when mean arterial blood pressure (MAP) = baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO2 (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%,, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO2. However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations. (Anesth Analg 2009;109:1576-83

Lung ventilation/perfusion SPECT in the artificially embolized pig.

Planar lung scintigraphy is a standard method used for the diagnosis of lung embolism, but it is hampered by the high incidence of nondiagnostic tests. Ventilation/perfusion SPECT may possibly improve this situation. The objective of this study was to compare planar lung scintigraphy with ventilation/perfusion SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl. METHODS: Sixteen anesthetized pigs were each injected with zero to 4 latex emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc-diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled macroaggregated albumin were injected intravenously followed by SPECT and, finally, planar scintigraphy. The ventilation background was subtracted from the perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P) quotient image set. RESULTS: The cylindric emboli caused artifacts in the ventilation images; therefore, these were excluded from the final analysis. However, for the planar perfusion images of these pigs, sensitivity and specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both. For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and specificity were 64% and 79%, respectively, for the planar modality, whereas SPECT yielded values of 91% and 87%, respectively. CONCLUSION: V/P SPECT may improve the diagnostic power of lung scintigraphy

Circulatory effects of hypoxia, acute normovolemic hemodilution, and their combination in anesthetized pigs

BACKGROUND: Because hemodilution decreases the oxygen-carrying capacity of blood, it was hypothesized that severe hemodilution would decrease the tolerance to alveolar hypoxia. METHODS: Hemodynamics, oxygen transport, and blood lactate concentrations were compared in ten pigs with normal hematocrit (33 +/- 4%), and ten hemodiluted pigs (hematocrit 11 +/- 1%; mean +/- SD) anesthetized with ketamine-fentanyl-pancuronium during stepwise decreases in inspired oxygen fraction (FIO2; 1.0, 0.35, 0.21, 0.15, 0.10, 0.05). RESULTS: Median systemic oxygen delivery (DO2SY) became critical (the DO2SY value when arterial lactate exceeded 2.0 mmol.l-1) at 10.4 ml.kg-1.min-1 (range 6.9-16.1) in hemodiluted animals and at 11.8 ml.kg-1.min-1 (5.9-32.2) in animals with normal hematocrits (NS). The relationship between mixed venous oxygen saturation and arterial lactate values was less consistent and median critical mixed venous oxygen saturation was higher (P < 0.05) in the hemodiluted group (35%, range 21-64), than in animals with normal hematocrits (21%, 7-68%). In animals with normal hematocrit, decreasing FIO2 from 1.0 to 0.10 resulted in a decrease in DO2SY from 26.3 +/- 9.1 to 9.3 +/- 3.9 ml.kg-1.min-1 (P < 0.01). Cardiac output did not change, systemic oxygen extraction ratio increased from 0.23 +/- 0.08 to 0.68 +/- 0.13 (P < 0.01), and arterial lactate from 0.9 +/- 0.2 to 3.4 +/- 3.0 mmol.l-1 (P < 0.05). Cardiac venous blood flow, as measured by retrograde thermodilution, increased from 5.7 +/- 2.9 to 12.6 +/- 5.7 ml.kg-1.min-1 (P < 0.01). When FIO2 was reduced to 0.05, three animals became hypotensive and died. In the second group, hemodilution increased cardiac output and systemic oxygen extraction ratio (P < 0.01). Cardiac venous blood flow increased from 4.1 +/- 1.7 to 9.8 +/- 5.1 ml.kg-1.min-1 (P < 0.01), and cardiac venous oxygen saturation from 22 +/- 5 to 41 +/- 10% (P < 0.01). During the subsequent hypoxia, cardiac output and DO2SY were maintained until FIO2 = 0.15 (DO2SY = 10.1 +/- 3.3 ml.kg-1.min-1). Cardiac venous blood flow was then 18.5 +/- 10.7 ml.kg-1.min-1 (P < 0.01), but in spite of this, myocardial lactate production occurred. At FIO2 = 0.10 (DO2SY = 7.7 +/- 3.0 ml.kg-1.min-1), arterial lactate concentration increased to 8.5 +/- 2.3 mmol.l-1 (P < 0.01), and most animals became hypotensive. All hemodiluted animals died when FIO2 was decreased to 0.05 (P < 0.01 when compared to animals with normal hematocrit). CONCLUSIONS: Systemic and myocardial lactate production occurred at similar systemic oxygen delivery rates in hemodiluted and nonhemodiluted animals. Mixed venous oxygen saturation may be a less reliable indicator of inadequate oxygen delivery during hemodilution