Chemical Cardioplegia Research Articles

WITHDRAWN: Cardioplegia and Cardiac surgery: A comprehensive literature review

Abstract Myocardial protection is an essential component of cardiac surgery. Cardioplegic solutions induce cardiac arrest in order to optimise operative conditions. Importantly, cardioplegia enhances myocardial recovery and improves clinical outcomes. There have been considerable advances in myocardial protection since the concept of chemical cardioplegia was first introduced in 1955. Methods can be characterised according to solution, temperature, additives and delivery methods. In spite of significant research, there is still no clear consensus on the cardioplegic method or solution associated with optimum clinical outcomes. This is a comprehensive and comparative overview of the available and upcoming methods in the field of myocardial protection.

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Myocardial Protection Era: From Valve Surgery to Heart Transplantation

Pro: Ischemic preconditioning has a myocardial protective effect during coronary artery bypass surgery

MYOCARDIAL PROTECTION has remained one of the main issues in the management of heart surgery. Since Bigelow brought the notion of myocardial protection into cardiac surgery in the 1950s, highly effective methods of myocardial protection during heart surgery have been developed, including hypothermia, chemical cardioplegia, and cross-clamp ventricular fibrillation.1 However, there is still a need to improve myocardial protection because of the increasing number of operations on older and higher risk patients. Ischemic preconditioning could be one option to give better preservation of heart tissue during operations.

Electroplegia: an alternative to blood cardioplegia for arresting the heart during conventional (on-pump) cardiac operation

Background. Aortic cross-clamping is contraindicated in patients with severe atherosclerosis of the ascending aorta, and administration of chemical cardioplegia may be cumbersome in these patients. In this study, we demonstrate an alternative method of achieving cardioplegia by electrical stimulation of the vagus nerve. Methods. In anesthetized canines, the left anterior descending coronary artery was reversibly ligated for 90 minutes, followed by cardiopulmonary bypass (CPB) and randomization to three groups (n = 8 each): (1) BCP group: 1 hour of intermittent hypothermic (4°C) blood cardioplegia infusion; (2) CPB group: 1 hour of CPB alone; (3) EP group (group receiving electroplegia): 1 hour of intermittent vagal stimulation (total of 60 20-second electrical stimuli at 40 Hz, 6 to 10 V) with adjunctive pyridostigmine (0.5 mg/kg), verapamil (50 μg/kg), and propranolol (80 μg/kg) to potentiate hyperpolarization and suppress ectopic escape beats. Results. The EP group achieved consistent intervals of arrest with 3.8 ± 1.2 escape beats per 20-second stimulation period. After 2 hours of reperfusion off CPB, the left anterior descending coronary artery segmental shortening was reduced from baseline in all groups, but the segmental shortening recovered to a greater extent in the EP group than in either the CPB or BCP group (2.4% ± 1.4% versus −1.3% ± 1.3% versus −4.0% ± 0.8%, p < 0.05). Infarct size (TTC stain, percentage of area at risk) was comparable among groups (EP: 20.9% ± 4.7%; CPB: 29.6% ± 3.2%; BCP: 25.1% ± 5.7%). Postischemic left anterior descending coronary artery endothelial function (percent maximum relaxation to acetylcholine) was depressed in the EP group (68.6% ± 7.6% versus 102.3% ± 6.4%, p < 0.05), but was comparable versus nonischemic circumflex function in the BCP group (77.1% ± 11.9% versus 100.4% ± 10.0%, p = 0.15) and the CPB group (93.8% ± 6.6% versus 93.3% ± 6.6%). Conclusions. Electroplegia achieves elective intermittent cardiac arrest, avoids hypothermia, chemical cardioplegia, and aortic cross-clamping, with physiological outcomes comparable to blood cardioplegia.

Organ Preservation, Vol. 37, No. 2 of International Anesthesiology Clinics.

Organ Preservation, Vol. 37, No. 2 of International Anesthesiology Clinics.Roysten D, ed. Philadelphia: Lippincott Williams & Wilkins, 1999. ISSN 0020-5907. 130 pages, $61.00. Although the title of the book may suggest the preservation of organs for transplantation, the authors’ objectives were to review molecular pathogenesis of organ dysfunction and scientific rationale for specific interventions and treatments of organ dysfunction associated with cardiac surgery. The book is composed of five chapters; the host defense system by cellular blood components, myocardial protection during cardiac surgery, pulmonary hypertension after cardiac surgery, the role of the intestines in postoperative morbidity, and renal preservation. The first chapter contains an in-depth description of the cellular host defense system and hemostasis contributed by neutrophils and platelets, respectively. The review of molecular interaction of inflammatory response and hemostasis is informative. It appears that the authors’ intention was to describe hemostasis as a part of inflammatory response or a host defense mechanism. However, a relatively weak description of the interaction of two systems gives an impression of one chapter with two isolated topics. The chapter on myocardial preservation describes mechanisms of myocardial stunning, determinants of coronary blood flow, and myocardial protection by chemical cardioplegia and ischemic preconditioning. Pulmonary hypertension observed during cardiac surgery and cardiac transplantation is described in the third chapter. Description of pathophysiology of pulmonary hypertension during and after cardiac surgery and cardiac transplantation is quite extensive. In addition, the rationale and mode of treatment including nitric oxide, prostacyclin, phosphodiesterase inhibitors, adenosine, adrenomedulin, and mechanical support are described. The effect of translocation of intestinal bacteria and endotoxin into the systemic circulation on the development of the systemic inflammatory response syndrome is described in the fourth chapter. In addition, the authors describe potential causes of mucosal hypoxia, various methodologies of monitoring mucosal perfusion status, and approaches to preventing postoperative gut-derived complications. The chapter on renal protection describes potential causes and interventions of postoperative renal dysfunction. The authors, however, do not comment on molecular mechanisms of renal dysfunction. Overall, this monograph describing organ dysfunctions associated with major surgery is easily readable for most clinical anesthesiologists. It is admirable that the authors tried to cover molecular mechanisms of specific organ dysfunction and relate to clinical complications and their interventions. There are two drawbacks in this book: 1) the other two major organ functions, namely central nervous system and pulmonary system, are not addressed and 2) the difficulty in combining molecular biology and clinical science results in superficial coverage of both areas. The authors, however, have achieved their objectives if they were able to deliver a scientific background of organ dysfunction to clinicians.

Perfluorochemical reperfusion yields improved myocardial recovery after global ischemia

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 °C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/ glulamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular strok? work index of 3.8 ± 2.3 × 10 3 erg/g (mean ± standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 ± 1.3 × 10 3 erg/g, significantly greater than that of the whole blood group ( p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 ± 1.6 × 10 3 erg/g, significantly increased over that of the nonenriched perfluorochemical group ( p < 0.01) and not different from values obtained in controls (19.2 ± 0.8 × 10 3 erg/g). In addition, perfluorochemical-reperfused hearts demonstrated superior maintenance ( p < 0.05) of adenosine triphosphate (2.08 ± 0.16 μmol/g) compared with the whole blood group (1.50 ± 0.19 μmol/g), whereas preservation of adenosine triphosphate in the enriched perfluorochemical group (2.99 ± 0.12 μmol/g) was significantly increased over that of the nonenriched perfluorochemical group ( p < 0.001 μmol/g) and not significantly different from that in controls (2.68 ± 0.17 μmol/g). Electron microscopy revealed notably improved preservation of ultrastructural architecture in perfluorochemical-treated hearts (with or without aspartate/ glutamate) compared with the whole blood group. We conclude that initial reperfusion of the postischemic myocardium with oxygenated perfluorochemical ameliorates the deleterious effects of whole blood reperfusion. In addition, amino acid enrichment, buffer supplementation, and chemical cardioplegia enhance this effect, allowing for complete functional recovery of the piglet myocardium after 12 hours of hypothermic ischemia.

Myocardial Loss of Glutamate after Cold Chemical Cardioplegia and Storage in Isolated Blood-Perfused Pig Hearts

Metabolic adaptation of the ischemic human heart includes release of lactate, augmented uptake of glucose and glutamate, together with increased release of citrate and alanine. In the present study exchanges of these metabolites were examined in relation to left ventricular function (LVF) in pig hearts during reperfusion after hypothermic cardioplegic-induced global ischemia and storage. Three groups of pig hearts were studied. Group I consisted of 11 hearts subjected to 9 minutes of warm ischemia prior to cold chemical cardioplegia with Bretschneider's cardioplegic solution (CCC), and hypothermic storage (HS), for a total of 180 minutes. Groups II and III, 8 hearts in each, were subjected to 90 and 180 minutes of CCC and HS, without precardioplegic warm ischemia. All hearts were reperfused in an isolated blood-perfused Langendorff model. Myocardial oxygen uptake and LVF were two-fold depressed in Group I compared to Groups II and III during the first 25 minutes of reperfusion. An increased uptake of glucose (p < 0.05) and augmented release of lactate (p < 0.01) and citrate (p < 0.001) were found during the reperfusion period in the hearts subjected to precardioplegic warm ischemia, indicating an increased total ischemic burden compared to Groups II and III. No significant changes in LVF or myocardial metabolism were noted between Groups II and III during reperfusion. In all three heart groups a substantial release or loss of glutamate was found at start of reperfusion, although in the preischemic state prior to cardioplegia pig hearts were found to extract glutamate from the circulation to an extent similar to that of the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of pre-existing ischemia on recovery from chemical cardioplegia. A study on pig hearts in an isolated blood-perfused model.

The impact of prior cardiac ischemia on recovery from chemical cardioplegia was investigated in pig hearts. Group I hearts were subjected to 9-min normothermic ischemia before the start of chemical cardioplegia. After 180 min of induced cardiac arrest, all hearts were reperfused and monitored for 120 min in a blood-perfused Langendorff model. Consistent with left ventricular performance, myocardial oxygen uptake was significantly lower in group I than in the other hearts during the first 60 min of reperfusion. Lactate elimination was significantly higher in group I at the start of reperfusion, but showed no intergroup difference after 25 min. Nor was intergroup difference found in left ventricular end-diastolic pressure, total myocardial flow or glucose extraction fraction during reperfusion. The mitochondrial ultrastructure was identical in the two groups before chemical cardioplegia. During cardioplegia it deteriorated in group I but normalized in group II. During reperfusion these circumstances were reversed. Although precardioplegic ischemia thus significantly impaired left ventricular performance during early recovery, with corresponding effects on metabolism and ultrastructure, stable performance during reperfusion indicated that the ischemic injury did not worsen.

Improved preservation of endothelial function at 4 degrees C.

Hypothermia combined with chemical cardioplegia is routinely used clinically for perioperative myocardial protection and for donor heart preservation. Profound hypothermia can have an adverse influence on post-preservation endothelial and myocardial functions. In this study, we investigated the effect of temperature on endothelial and myocardial functions following global cardiac ischaemia in the isolated rat heart. A 5-hydroxytryptamine (5-HT)-induced increase in coronary flow was used as a selective probe to assess endothelial function, while myocardial function was measured by a working rat heart model. After recording control observations for endothelial and myocardial functions, hearts were kept ischaemic for 30 or 60 min without cardioplegia (groups 1 and 2, respectively) and for 60, 90 or 120 min following a single infusion of St. Thomas' Hospital solution (groups 3, 4 and 5, respectively). In each group, hearts were kept ischaemic at 20 degrees C or at 4 degrees C (n = 12 in each group). Endothelial and myocardial functions were reevaluated and compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia.

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous Warm Blood Cardioplegia: A New Technique for Myocardial Protection

Hypothermia is used to prolong the safe period of ischemic arrest by reducing the heart's oxygen demands. Due to this effect, hypothermia has been the fundamental component of most methods of myocardial protection during cardiac surgery. However, hypothermia has a number of unwanted side effects, such as detrimental effects on enzyme function, energy generation, and cell membranes. Since electromechanical arrest accounts for 90% of myocardial oxygen consumption, arresting the heart with chemical cardioplegia will reduce O2 consumption dramatically. Therefore, if the resting (arrested) heart is continuously perfused with oxygenated blood cardioplegia, one can easily provide the remaining 10% of O2 that it requires. Under these conditions, the need for hypothermia becomes questionable. In this paper, we describe the perfusionist's experience using the antegrade and retrograde technique of continuous warm blood cardioplegia.

Myocardial protection by simple systemic hypothermia without aortic occlusion

Systemic hypothermia at 25 degrees-28 degrees C without chemical cardioplegia was used in 908 patients undergoing coronary artery bypass grafting. Local coronary artery flow was interrupted only during grafting of a distal anastomosis. Systemic perfusion pressure was maintained at 80-100 mmHg, hematocrit at 20%-25%, and pCO2 and pH were monitored during hypothermia according to the alpha-stat principle, while the left ventricle was vented routinely. Proximal anastomoses were performed just before extracorporeal circulation was started by only partially occluding the ascending aorta. Preoperatively 61.9% of the patients had had a myocardial infarction, and 44% had unstable angina. In 14% a severe lesion of the main stem of the left coronary artery was present. Left ventricular function was moderately depressed in 25% and severely depressed in 8% of the patients. Forty-eight patients (5.3%) were aged 70 years or older. The mean number of grafts placed per patient was 3.3. Perioperative myocardial infarction occurred in 3%. Death due to left ventricular failure occurred in 0.4%. No left ventricular assist devices were needed; an intra-aortic balloon pump was used in 1%; positive inotropic support was required in 3.8% of the patients. These results indicate that systemic hypothermia alone provides safe myocardial protection and in certain cases may be the method of choice, particularly if aortic cross clamping or administration of cardioplegic solution is contraindicated. In addition, this method provides rapid revascularization of a severely ischemic zone, as present after unsuccessful PTCA procedures.

Myocardial preservation during ischemia and reperfusion

Protection of the myocardium during cardiac surgery is necessary because of two distinctly different forms of injury: ischemia during cross-clamping of the aorta and secondary destructive phenomena during reperfusion. The primary injury of ischemia is caused by a combination of inadequate or no delivery of substrate and inadequate or no flow, which prevents the removal of toxic intermediary and end products of anaerobic metabolism. The secondary injury, that due to myocardial reperfusion after prolonged ischemia, has been shown in experimental models to accentuate ischemic injury, hasten cell death, and thus may extend infarct size. Protection of the myocardium from the primary ischemic injury with chemical cardioplegia was first introduced by Melrose et al.’ in 1955. Since then extensive animal studies2e5 have provided not only a foundation for understanding the physiologic and metabolic derangements in myocardium during ischemia but also the basis for formulating the various cardioplegic solutions for clinical use. Roe et a1.6 were among the first to describe a large clinical experience with single-dose, crystalloid, hypothermic potassium cardioplegia, which yielded very low morbidity and mortality. Tylers et a1.,7 Conti et al.,s and Adams et al9 reported similar results when multidose cardioplegia was used. The use of oxygenated blood as a vehicle for cardioplegic arrest was advocated by Follette et al.l” in 1978. The superiority of sanguineous cardioplegia was then demonstrated in several clinical studies”-l3 both in terms of longer cross-clamping time and lower perioperative

The protection of the ischemic myocardium: Surgical success v clinical failure?

I N THE EARLY 1970s both cardiac surgeons and clinical cardiologists were regularly confronted with the hazards of myocardial ischemia. In the surgeons’ case, the ischemia was global, the whole human heart being deprived of blood in order to provide a bloodless, nonbeating organ on which to operate. Fatal, irreversible ischemic contracture, the so-called “stone heart,“’ was not uncommon. Surgeons attempted to complete their work in less than one hour, and biochemists were “challenged”2-4 to find an answer to the stone heart. Work on the surgically abandoned concept of hypothermic chemical cardioplegia’-’ was restarted in Europe9-14 and North America, ‘*Jo even though many surgeons remained skeptical. As late as 1976 Effler17 rejected “hibernation” with “drug cocktails,” saline slush (he recommended surgeons to try putting their feet in a bucket of ice slush in order to appreciate the discomfort), and coronary perfusion as being “troublesome and hazardous.” He wondered whether there really was a “true need for myocardial preservation.” However, in less than a decade the problems of surgical ischemia were effectively conquered, and crystalloid and blood cardioplegic solutions were in use internationally. One formulation, the St Thomas’ Hospital Cardioplegic Solution (Plegisol; Abbott, North Chicago, IL), developed by the author and his colleagues, even received the approval of the United States Food and Drug Administration. Many surgeons found that they were able to safely subject hearts to ischemic times of three, four, and even five hours; postoperative recoveries were improved, and mortality figures fell. Cardioplegic solutions were soon applied in cardiac transplantation, and preservation times for human hearts in excess of 15 hours were reported.‘* By 1986, the ravages of ischemia were no longer the major concern of most cardiac surgeons. The skepticism of the surgeons in the early 1970s was well compensated for by the optimism of the cardiologists. Several influential and exciting studies were published, notably one by Maroko et al in 197 1 l9 in which he reported that a number of drugs, including beta blockers, when given to dogs whose coronary arteries had been ligated, acted to reduce the size of an evolving infarct. The elimination of the threat of regional myocardial ischemia seemed near at hand, and with understandable optimism, Dr Eugene Braunwald was able to state in 1974:

Decreased incidence of supraventricular arrhythmias achieved by selective atrial cooling during aortic valve replacement.

Inadequate atrial hypothermia and subsequent ischemic injury have been recognized as the major causes of supraventricular arrhythmias (SVAs) and conduction defects following cold chemical cardioplegia. This study was designed to assess the effects of right atrial cooling (15 degrees-20 degrees C) during cardioplegic arrest upon the incidence of postoperative SVAs and conduction defects in 40 consecutive patients undergoing isolated aortic valve replacement. Atrial preservation was ensured by combining systemic (24 degrees C) and topical hypothermia with snared double caval cannulation during arrest. Myocardial temperatures in the right atrial septum and anterior wall of the right ventricle were recorded before and after each cardioplegic infusion and upon release of caval tapes. Postoperatively, the incidence of SVAs and conduction defects was assessed by continuous rhythm monitoring, bipolar atrial electrograms and, in ten patients, 24-h Holter recordings during the first postoperative day. With the venae cavae snared, temperatures in the right atrial septum were not significantly different from those measured simultaneously in the right ventricle. Release of caval tapes resulted in right atrial temperatures increasing to systemic temperature (from 17.1 +/- 2.9 degrees C to 25.9 +/- 5.6 degrees C [m +/- SD]; P less than 0.01). Atrial rewarming between cardioplegic infusions did not exceed 2.9 degrees +/- 3.2 degrees C. Postoperatively, four patients (10%) developed sustained atrial fibrillation. One additional patient had a single episode of paroxysmal atrial fibrillation and two patients experienced asymptomatic episodes of junctional rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart

The quality of myocardial protection during cardiac arrest in cardiac operations was investigated in 310 patients. Eighty patients underwent aortic valve replacement and 230 had coronary artery bypass grafting. Four different cardioplegic solutions (Kirsch, Bretschneider, St. Thomas' Hospital, and Hamburg) and the method of induced fibrillation were tested by ultrastructural analysis of the degree of ischemic injury at the end of the cardiac arrest period. Hypothermia was identical in all five groups. In this study, subendocardial and subepicardial needle biopsies were evaluated by a standardized scoring system. Chemical cardioplegia produced mainly moderate ultrastructural injury independent of the time of ischemia. Kirsch cardioplegia and the intermittent fibrillation procedure produced ischemic injury of greater and unpredictable severity. Only with Kirsch cardioplegia was a correlation observed between the duration of intraoperative arrest and the degree of injury, which is indicative of a lack of myocardial protection. The tolerance to ischemia was significantly better in patients undergoing bypass grafting than in those with aortic valve disease and therefore longstanding hypertrophy. In conclusion, the Bretschneider, St. Thomas' Hospital, and Hamburg solutions provide satisfactory myocardial protection but are not able to completely prevent myocardial ischemic injury. Kirsch cardioplegia and the intermittent fibrillation procedure provide insufficient myocardial protection. Patients with left ventricular hypertrophy are at a greater risk during cardiac operations than patients undergoing coronary bypass operations.

Rod-like intramitochondrial inclusions after hypothermic chemical cardioplegia during cardiac operations

Rod-like intramitochondrial inclusions in the myocardial cells were observed after hypothermic chemical cardioplegia in three out of 20 patients who underwent coronary bypass operations. They were not seen in another group of 20 patients who underwent an aortic valve replacement operation in whom only topical cooling was used for myocardial protection. The occurrence of rod-like intramitochondrial inclusions could not be correlated with other signs of ischemic myocardial injury. X-ray microanalysis did not reveal any inorganic substance in the intramitochondrial inclusions. Therefore, we believe that their occurrence was not related to the calcium paradox phenomenon, a feared complication of cardiac operations.

The effect of hypothermia and chemical cardioplegia on the mobilization of noradrenaline from the heart during post-ischaemic reperfusion

The effect of hypothermia and chemical cardioplegia on the mobilization of noradrenaline from the heart during post-ischaemic reperfusion

Substance P- and leu-enkephalin-immunoreactive nerves before and after myocardial ischaemia, hypothermic chemical cardioplegia and reperfusion injury during open-heart surgery

During open-heart surgery, myocardial biopsies were obtained before the start of extracorporeal circulation (from the right auricular appendage) and after weaning from the pump (from the right atrium), and processed for immunocytochemical demonstration of substance P- and leu-enkephalin-immunoreactive nerve fibres and for electron microscopy. Substance P-immunoreactive nerves were seen around blood vessels, between myocardial cells and forming large glomerulus-like loops, but were not numerous. Leu-enkephalin-immunoreactive nerves were very sparse. We therefore believe that both nerve types primarily are modulatory axons. In the post-weaning specimens, nerves of both types were more numerous (attributable to the different site of biopsy), and no change was seen in the immunofluorescence reaction. The ultrastructure (all types) of nerve terminals was well preserved, although myocardial damage was obvious in many specimens. Cardiac nerves, including peptidergic nerves, thus seem to be relatively resistant to ischaemia, hypothermic chemical cardioplegia and reperfusion injury.

Protective effects of cardioplegia on diastolic function of hypertrophied rat hearts after hypothermic ischaemic arrest.

This study was undertaken to assess the effects of hypothermia and chemical cardioplegia on the functional recovery of hypertrophied non-failing rat hearts subjected to an extended period of global ischaemia. Left ventricular hypertrophy was produced by constriction of the abdominal aorta. Hearts were studied an average of 8 weeks following this procedure. Sham-operated animals served as controls. Twenty-nine isolated isovolumic perfused rat heart preparations were then subjected to 2 h of ischaemic arrest at 15-18 degrees C followed by 45 min of normothermic reperfusion. In one series of hearts (8 sham, 8 hypertrophied), myocardial protection consisted of hypothermia alone. In another series (6 sham, 7 hypertrophied), repeated infusions of cardioplegic solution at 30-min intervals throughout arrest were added to hypothermia. Hypothermia alone resulted in a similar preservation of contractility as evidenced by the recovery of dp/dtmax/left ventricular (LV) systolic pressure after 45 min of reperfusion (91.6 +/- 5.9% of control values in sham vs 78.6 +/- 6.5% in hypertrophied hearts). Conversely, the recovery of compliance was much more impaired in hypertrophied hearts as indicated by a significantly higher percentage of increase in post-ischaemic LV diastolic pressure (DP) (at 45 min of reperfusion: 243.8 +/- 27.5% of control values vs 167.1 +/- 23.8% in sham, P less than 0.05). The addition of cardioplegia improved the preservation of contractility in both groups but its major effect was to normalize the recovery of compliance in hypertrophied hearts so that post-ischaemic LVDP values were no longer different from those recorded in normal hearts (at 45 min of reperfusion: 102.1 +/- 32.8% vs 98.5 +/- 14.2% of pre-ischaemic values respectively).(ABSTRACT TRUNCATED AT 250 WORDS)