Experimental surgery needs a pharmacological approach that can interfere with cardiac function

Barbieri, Alberto

Farinetti, Alberto

Giuliani, Enrico

Manenti, Antonio

Mattioli, Anna Vittoria

English

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbitsAnn. Ital. Chir., 88, 3, 2017 1Ann. Ital. Chir., 2017 88, 3: ???-???pii: 0000000000000Pervenuto in Redazione Maggio 2017. Accettato per la pubblicazioneLuglio 2017Correspondence to: Alberto Farinetti, MD, Surgical, Medical and DentalDepartment of Morphological Sciences related to Transplant, Oncology andRegenerative Medicine, University of Modena and R.E., Via del pozzo 71,41100 Modena Italy (e-mail: alberto.farinetti@unimore.it)Enrico Giuliani*, Antonio Manenti**, Alberto Barbieri*, Alberto Farinetti**, Anna Vittoria Mattioli**University of Modena and Reggio Emilia, Italy*Department of Medical and Surgical Sciences**Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative MedicinePropofol: a safe anaesthetic drug in experimental cardiac surgery in rabbitsACKGROUND: Experimental surgery needs a pharmacological approach that can interfere with cardiac function.CASE REPORT: In a animal model of regenerative medicine of myocardium we use an anaesthesiological  protocol thatincluded Propofol, a benzodiazepine (Midazolam) and an alpha-2 adrenergic agent. RESULTS: In a group of 15 rabbits undergoing cardiac surgery we reported 1 arrhythmic complication during stem cellinjection.DISCUSSION: The functional cardio- respiratory depressor activity of Propofol was compensated by alpha-2 adrenergicdrugs, avoiding serious complications. We hypothesize that the functional cardio-respiratory depressor of different anaes-thesiological drugs can be reversed by the contemporary administration of with adrenergic agents.KEY WORDS: Arrhythmias, Cardiac ischemia, Cardiovascular toxicity, PropofolLav. 2739Case ReportThe experimental protocol included 15 male adult “NewZealand white rabbits”, with a mean weight of 4.1 kg.The surgical procedure consisted in a left antero-lateralthoracotomy, pericardiotomy, and exposure of the anteri-or wall of the left ventricle. The anterior descending coro-nary artery, identified in its third proximal segment, wasoccluded for a time ranging from 4 to 5 minutes, untilan area of myocardial tissue of 1-1.5 cm in diameterappeared ischemic. At the end of the surgical procedure,a complete re-expansion of the left lung was obtained withthe simple aid of a temporary pleural aspiration 3.The animals were subdivided in three groups of five rab-bits each:– Sham;– Intravenous injection of BM stem cells;– Intra-myocardial injection of BMSC.  The anesthesiological protocol included three drugs, abenzodiazepine (Midazolam), an alpha2-adrenergic agent,and an anaesthetic (2,6, -diisopropilfenol - Propofol),selected for their respective action of sedation, alpha-2mimetic activity and analgesia. The first two drugs wereIntroduction The choice of animals for cardiovascular experimentalstudies depends: first, on their physiological and anatom-ical characteristics; then, on the size of the animal, stab-ulation cost, human protective affection, and on anaes-thesiological and monitoring facilities. In our experi-mental study on cardiac ischemia/reperfusion damage andsubsequent treatment with homologous bone marrowmesenchymal stem cells (BMSC), we selected rabbits fortheir similarities with human coronary arteries and withpatho-physiology of immunological system 1,2. However, these animals have a particular pharmaco-anaes-thesiology, in relation to their susceptibility to stressor agentsand to particular sensibility to some anaesthetic agents.administered at the induction of anaesthesia, while thethird was continued throughout the entire surgery.Animals were sedated by an intra-muscolar injection of1 mg/kg of Midazolan, associated with Medetomidyne1 mg/kg. A marginal auricular vein was cannulated witha standard 22-Gauge intravenous catheter and an initialdose of 2.5 mg/kg Propofol solution was administrated2 minutes before surgical positioning. The depth ofanaesthesia was maintained with equivalent doses admin-istered every 5 minutes throughout the entire surgery.The spontaneous respiratory activity was assured with asimple muzzle musk connected with a bag valve systemof 0.5 litre using room air, enriched with a 50% O2,even during the one lung ventilation phase. The intra-operative monitoring consisted of a continu-ous ECG recording and of a pulse oximetry. Hypotensionand blood losses were compensated by saline infusion. Evaluation of Side effects of anaesthesia was assessed dur-ing and early after surgery (within the first 12 hours).We monitored the following parameters: – respiratory depression, requiring manual respiratoryassistance and/or an increased oxygen supply;– severe bradycardia or arrhythmia (recorded by ECG);– death.All animals received care in compliance with theEuropean Convention on Animal (Directive 2010/63/EUof  22.09.2009).  The protocol was approved by Research Animal Careand Use Committee of the University of Modena andReggio Emilia (Italy) (prot. # 25, 18/03/2008 and prot.#83, 25/ 09/2009).Results and DiscussionWe reported 3 episodes of reversible ventricular tachy-cardia (VT) and one episode of ventricular fibrillationsuccessfully cardioverted during induction of ischemia.We registered only one fatal complication (6.66%), rep-resented by a ventricular arrhythmia developed duringintra-myocardial BMSC injection. It is well known thatthe direct intramyocardial administration of BMSC caninduce a transient pro-arrhythmic effect. 4The anaesthesiological protocol we tested demonstrateda proper action of sedation and myo-relaxation, withouthindering the spontaneous respiration 5. The depth ofanalgesia was proved by suppression of any muscularreaction to surgical stimuli, which are potential stressorsfor rabbit. Neither administration of anti-arrhythmicdrugs, such as lidocaine, nor invasive monitoring of thearterial pressure was necessary, considering the absenceof cardio-circulatory adverse effects 6. Interestingly, thisvenous anaesthesiological protocol avoided the use ofneuromuscular blocking agent 7. The correct oxygena-tion, recorded throughout the entire surgical time andobtained with enriched air, avoided oro-tracheal intuba-tion, complex manoeuvre in rabbits. Moreover, the rapideffects of Propofol allowed a quick anaesthesiologicalrecovery.  In conclusion, our experience in rabbit experimental car-diac surgery indicates Propofol as a suitable analgesic agentfor the induction of anaesthesia and its maintenance.Propofol mild cardio-respiratory depressing action may beeffectively balanced associating an alpha2–adrenergicagent8. RiassuntoPREMESSA.: La chirurgia sperimentale richiede un approc-cio farmacologico che può interferire con la funzione car-diaca.METODI:In un modello animale di chirurgia rigenerativadel miocardio abbiamo utilizzato un protocollo aneste-siologico che includeva Propofol, una benzodiazepina(Midazolam) e un alfa2-adrenergico.RISULTATI:In un gruppo di 15 conigli sottoposti a chi-rurgia cardiaca abbiamo osservato 1 complicanza aritmi-ca letale durante la somministrazione intramiocardica dicellule staminali.DISCUSSIONE. L’azione di depressione della funzione car-dio respiratoria del Propofol è stata compensate da far-maci con attività alfa2-adrenergica che hanno ridottonotevolmente le complicanze aritmiche. Ipotizziamo che l’azione di depressione della funzionalitàcardio respiratoria di farmaci anestesiologici utilizzati nel-la chirurgia sperimentale cardiaca nel coniglio possa esse-re controllata dalla somministrazione contemporanea diagenti adrenergici.References1. Podesser B, Wollenek G, Seitelberger R et al.: Epicardial branch-es of the coronary arteries and their distribution in the rabbit heart:the rabbit heart is a model of regional ischemia. Nat Record, 1997;247: 521-27. 2. Zhang J, Qin XY, Wan YF, Yuan C: Establishment of a reper-fusion model in rabbits with acute myocardial infarction. Cell BiochemBiophys, 2011; 60:249-58.3. Farinetti A, Lonardi R, Barbieri A, Giuliani E, Pennella S, PozzaM et al.: Surgical approach to intramyocardial administration of bonemarrow stem cells in an animal model. Ann It Chir, 2013; 84: 455-58. 4. Pennella S, Reggiani Bonetti L, Migaldi M, Manenti A, LonardiR, Giuliani E, Barbieri A, Farinetti A, Mattioli AV: Does stem celltherapy induce myocardial neoangiogenesis? Histological evaluation inan ischemia/reperfusion animal model. J Cardiovasc Med, 2017;18(4): 277-82. doi: 10.2459/JCM.0000000000000357.5. Ferrando C, Aguilar G, Piqueras L, Moreno J, Belda FJ:Sevofluorane, but not propofol, reduces the lung inflammatory responseand improves oxygenation in an acute respiratory distress syndromemodel: A randomized laboratory study. Eur J Anaesthesiol, 2013; 30:455-83.E. Giuliani, et al.2 Ann. Ital. Chir., 88, 3, 20176. Deschk M, Wagatsuma JT, Araùjo MA, Santos GG, AbimussiCJ, Siqueira CE, Motta JC, Pern SH, Santos PS: Continuous infu-sion of propofol in calves: Bisprectal index and hemodynamic effects.Vet Anaesth Analg, 2016; 43: 309-15.7. Reupke V, Walliser K, Perl T, Kimmina S, Schraepler A,Quintel M, Kunze-Sziks Zay N: Total intravenous anaesthesia usingpropofol and sulfentanil allows controlled long-term ventilation in rab-bit without neuromuscular blocking agents. Lab Animal, 2016;0023677216660337. 8. Hedenquist P, Edner A, Jensen-Waern M: Anaesthesia withmedetomidine premedicated New Zeland white rabbits: A comparisonbetween intravenous sulfentanil-midazolan and isoflurane anaesthesiafor orthopedic surgery. Lab Anim, 2014; 48:155-63. Ann. Ital. Chir., 88, 3, 2017 3Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits

Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits

https://iris.unimore.it/bitstream/11380/1166921/1/2739_Giuliani%20bozze.pdf

Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits

Abstract

Similar works

Full text

Available Versions

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia