Experimental evaluation of hypothermic intermittent coronary perfusion.

The recovery of the myocardial contractility of blood-perfused papillary muscle from the rabbit hearts was used to determine if hypothermia would minimize the myocardial injury associated with intermittent aortic cross-clamping (IACC). Continuous normothermic coronary perfusion for 2 hours with either cross circulation or a membrane oxygenator had only minimal adverse effects on contractility. None of the hearts tolerated normothermic IACC (45 minutes of anoxia and 10 minutes of reperfusion, repeated twice), When the myocardial temperature was reduced to 32 degrees C., the recovery following IACC was 41.25 +/- 11.21 percent (n=8). With hypothermia of 28 degrees C., it was 70.43 +/- 13.03 percent (cross circulation group, n=7) or 68.36 +/- 13.11 percent (membrane oxygenator group, n=7). If the hearts were cooled to 24 degrees C., the recovery of the myocardial contractility following IACC was 90.95 +/- 5.42 percent (n=11). The improvement of the degree of recovery by hypothermia was statistically highly significant (p less than 0.005). Creatine phosphokinase (CPK) and isoenzymes (CPK-MB) were also measured in some groups, but the results warrrant further studies before they can be correlated with the myocardial function.     

Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man

We report observations on ultrastructural and cytochemical changes in the myocardium after hypothermic protection in 21 patients who underwent cardiac operation. Two general categories of hypothermic protection were studied. (1) topical cooling during anoxic arrest and moderate general hypothermia (10 patients with aortic valve replacement, Group 1) and (2) intermittent perfusion during moderate general hypothermia combined with topical cooling (11 patients with multiple valve replacement, Group II). Transmural left ventricular biopsies were taken at the start of the cardiopulmonary bypass and shortly after the end of aortic cross-clamping. In Group I (cross-clamp time, 51 +/- 12 minutes) only minor pathologic changes of the myocardial fine structure were found, with no differences among the left ventricular layers. In most mitochondria, structure remained intact but the mitochondrial granules disappeared. Cytochrome-c-oxidase activity was unchanged. In Group II (total cross-clamp time, 83 +/- 16 minutes) the subendocardium was well preserved. Slight subcellular damage comparable with that of resulting from topical cooling was seen in all hearts even after a total cross-clamp period of 106 minutes. Cytochrome-c-oxidase activity was unchanged. In the subepicardium, however, a positive correlation was found between the severity of ultrastructural damage and total cross-clamp time (p less than 0.05). Matrix clearing, damage to the cristae and the mitochondrial membranes, and nuclear abnormalities occurred when the aorta was cross-clamped for morethan 60 minutes. Cytochrome-c-oxidase activities decreased in these samples. It is concluded that: (1) no significant subcellular injury was found in hearts cooled topically during 1 hour of anoxic arrest; and (2) in hearts protected by intermittent perfusion during moderate general hypothermia and additional external cooling, the subendocardium was well preserved for anoxic periods of up to 106 minutes. However, after 60 minutes of aortic cross-clamping subcellular damage increased progressively in the subepicardium.     

Noncoronary collateral myocardial blood flow.

This study shows that noncoronary collateral flow occurs in normal hearts after chronic coronary occlusion and with left ventricular hypertrophy in variable amounts (0.2 to 16 ml/100 gm/min). Luminal--left ventricular flow is greatest when the heart is arrested by aortic cross-clamping, falls significantly when perfusion pressure is lowered to 50 mm Hg, and increases slightly when blood viscosity is reduced (hemodilution). Our findings indicate that the heart which is arrested by aortic cross-clamping may not be anoxic.     

Effect of Hypothermic Anoxic Cardioplegia on Myocardial Contractility

A study was undertaken to ascertain the protective effect of topical hypothermia on the anoxic heart. The presence or absence of myocardial damage was judged by myocardial contractility. The papillary muscle of an excised rabbit heart was detached from the mitral annulus and interposed between a fixed point and a force/displacement transducer. The maximal net developed tension (T_Nmax) of the papillary muscle with normothermic coronary perfusion was used as an index of myocardial contractility. With each temperature drop of 10°GC, the anoxia time that resulted in the same recovery level of T_Nmax was prolonged by a factor of 2.8. A nomogram was constructed correlating percent of myocardial recovery seen with different degrees of myocardial hypothermia during various anoxic periods. Optimum protection was noted at a myocardial temperature of 18°GC.     

Is protection of ischemic neonatal myocardium by cardioplegia species dependent?

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children, resulting in poor postischemic recovery of function and increased mortality. The relative susceptibilities to ischemia modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused neonatal (3- to 4-day-old) rabbit and pig hearts. Hearts were perfused aerobically with Krebs buffer solution in the working mode for 30 minutes and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2 followed by hypothermic (14 degrees C) global ischemia (rabbits 2, 4, and 6 hours; pigs 2 and 4 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic aortic flow was measured. Hypothermia alone provided excellent protection of the ischemic neonatal rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 91% +/- 4% and 87% +/- 5% (mean +/- standard deviation) of its preischemic value. Recovery after 6 hours of ischemia was depressed to 58% +/- 9% of its preischemic value. Ischemic neonatal pig hearts protected with hypothermia alone recovered 94% +/- 3% of preischemic aortic flow after 2 hours; none was able to generate flow after 4 hours. St. Thomas' Hospital solution No. 2 decreased postischemic aortic flow after 4 hours of ischemia in rabbit hearts from 87% +/- 5% to 70% +/- 7% (p less than 0.05, hypothermia alone versus hypothermia plus cardioplegia) but improved postischemic recovery of aortic flow in pig hearts after 4 hours of ischemia from 0 to 73% +/- 13% (p less than 0.0001, hypothermia alone versus hypothermia plus cardioplegia). This effect was dose related in both species. We conclude that the neonatal pig heart is more susceptible to ischemia modified by hypothermia alone than the neonatal rabbit and that St. Thomas' Hospital solution No. 2 improves postischemic recovery of function in the neonatal pig but decreases it in the neonatal rabbit. This species-dependent protection of the neonatal heart may be related to differences in the extent of myocardial maturity at the time of study.     

Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation

Abstract

Objectives. The aim of the study was to investigate if adequate preservation of coronary artery endothelium-dependent relaxation and contractility may be obtained after 8?hours of non-ischemic heart preservation. Design. Porcine hearts were perfused for 8?hours at 8?°C, either in cycles of 15?minutes perfusion and 60?minutes non-perfusion, or by continuous perfusion. The perfusate consisted of a cardioplegic, hyperoncotic nutrition solution with oxygenated red cells, and the perfusion pressure was 20?mmHg. In organ baths, coronary artery segments from the preserved hearts were studied and compared to fresh controls. Results. Endothelium-dependent relaxation and contractility were fully preserved after both intermittent and continuous perfusion, as compared to fresh controls. No myocardial edema was seen; water content of the myocardium was 79.5?±?0.2%, 79.0?±?0.4% and 79.0?±?0.3% (ns) for fresh controls, intermittently perfused, and continuously perfused hearts, respectively. Conclusion. Intact endothelial and contractile function of coronary artery may be obtained after 8?hours of non-ischemic heart preservation.     

Age-related changes in the ability of hypothermia and cardioplegia to protect ischemic rabbit myocardium

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children; poor postischemic recovery of function and increased mortality may result when this method of myocardial protection is used in children. The relative susceptibilities to ischemia-induced injury modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused immature (7- to 10-day-old) and mature (6- to 24-month-old) rabbit hearts. Hearts were perfused aerobically with Krebs-Henseleit buffer in the working mode for 30 minutes, and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2, followed by hypothermic (14 degrees C) global ischemia (mature hearts 2 and 4 hours; immature hearts 2, 4, and 6 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic function was measured. Hypothermia alone provided excellent protection of the ischemic immature rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 97% +/- 3% and 93% +/- 4% (mean +/- standard deviation) of the preischemic value. Mature hearts protected with hypothermia alone recovered only minimally, with 22% +/- 16% recovery of preischemic aortic flow after 2 hours; none were able to generate flow at 4 hours. St. Thomas' Hospital solution No. 2 improved postischemic recovery of aortic flow after 2 hours of ischemia in mature hearts from 22% +/- 16% to 65% +/- 6% (p less than 0.05), but actually decreased postischemic aortic flow in immature hearts from 97% +/- 3% to 86% +/- 10% (p less than 0.05). To investigate any dose-dependency of this effect, we subjected hearts from both age groups to reperfusion with either Krebs solution or St. Thomas' Hospital solution No. 2 for 3 minutes every 30 minutes throughout a 2-hour period of ischemia. Reexposure to Krebs solution during ischemia did not affect postischemic function in either age group. Reexposure of immature hearts to St. Thomas' Hospital solution No. 2 caused a decremental loss of postischemic function in contrast to incremental protection with multidose cardioplegia in the mature heart. We conclude that immature rabbit hearts are significantly more tolerant of ischemic injury than mature rabbit hearts and that, unexpectedly, St. Thomas' Hospital solution No. 2 damages immature rabbit hearts.     

Myocardial ultrastructural changes during extracorporeal circulation wtih anoxic cardiac arrest and its prevention by coronary perfusion. Experimental study.

This experimental work has been carried out with the aim of studying the ultrastructural myocardial changes caused by prolonged anoxic cardiac arrest during cardiopulmonary bypass, and their prevention by means of two different techniques of coronary perfusion--systemic-pressure continuous and low-pressure intermittent perfusion. After 30 minutes of cardiac anoxia, the ultrastructural changes of the myocardial cell were reverted to normal by coronary perfusion; when anoxic cardiac arrest was prolonged up to 60 minutes there was severe myocardial damage, with marked mitochondrial changes and dehiscence of intercalated discs, which persisted in spite of restoring coronary flow. These morphological data were in accordance with the fact that no dog which underwent anoxic cardiac arrest for 60 minutes recovered. Both intermittent and continuous coronary perfusion were effective in preventing anoxic damage; cardiac muscle cells were better preserved by low-pressure intermittent perfusion than by systemic-pressure continuous perfusion, which caused intracellular and intramitochondrial oedema.     

Mepacrine, a phospholipase inhibitor. A potential tool for modifying myocardial reperfusion injury

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.     

Safety of prolonged aortic clamping with blood cardioplegia. I. Glutamate enrichment in normal hearts

This study compares the protection provided by prolonged (4 hours) aortic clamping with glutamate-enriched potassium blood cardioplegia (n = 8) to (1) prolonged (4 hours) aortic clamping with multidose potassium blood cardioplegia without glutamate (n = 4), (2) 4 hours of continuous perfusion of the beating empty heart (n = 7), and (3) 15 minutes of normothermic ischemia (n = 10). According to measurements of myocardial oxygen uptake, left ventricular compliance, left ventricular contractility, and stroke work performance, no statistical difference could be detected between those hearts receiving blood cardioplegia either with or without glutamate enrichment. In both of these groups, myocardial protection was excellent, as demonstrated by the following: postischemic myocardial oxygen uptake 43% (p less than 0.05) above control, 95% +/- 6% recovery of the left ventricular compliance, a 97% +/- 5% return of the left ventricular contractility, and a 91% +/- 6% recovery of stroke work index. Contrary to the excellent recovery of those hearts receiving blood cardioplegic protection, those hearts undergoing 4 hours of continuous perfusion showed a 45% +/- 16% (p less than 0.05) loss of left ventricular compliance and a 72% +/- 8% (p less than 0.05) recovery of stroke work index; those hearts experiencing 15 minutes of normothermic ischemia showed a 74% +/- 6% (p less than 0.05) return of left ventricular compliance, a 30% +/- 5% (p less than 0.05) decrease in contractility, and a 56% +/- 5% (p less than 0.05) recovery of postischemic left ventricular stroke work.     

Is Reperfusion Injury from Multiple Aortic Cross-Clamping a Current Myth of Cardiac Surgery?

Four hundred eighty adult patients undergoing cardiac operations had systemic and topical hypothermic anoxic arrest supplemented with potassium chloride pharmacological cardioplegia in a prospective randomized study. Group 1 (217 patients) had continuous aortic cross-clamping and one single anoxic arrest period during the cardiac portion of the operation which resulted in a transmural myocardial infarction rate of 8.3%, myocardial “injury” incidence of 12.4%, 4.6% cardiac-related deaths, 11.5% and 24.8% severe and malignant ventricular arrhythmias, 21.7% rate of severe vasopressor usage, a mean group serum glutamic oxaloacetic transaminase (SGOT) of 140 ± 39 IU, and a mean group lactic dehydrogenase (LDH) of 636 ± 78.2 IU. Group 2 (263 patients) had intermittent aortic cross-clamping with multiple reperfusion intervals, which resulted in a significantly lower incidence of transmural myocardial infarction at 1.9% (p < 0.01), rate of myocardial injury at 5.66% (p < 0.02), number of cardiac deaths at 0.76% (p < 0.02), 8.7% and 16.0% severe and malignant ventricular arrhythmias (p < 0.01), severe vasopressor utilization rate of 14.3% (p < 0.05), mean group SGOT at 72.0 ± 3.1 IU (p < 0.01), and mean group LDH at 471.0 ± 12.3 IU (p < 0.05) than Group 1. These results do not support the contention that intermittent aortic cross-clamping in conjunction with hypothermia and pharmacological cardioplegia leads to increased clinical cardiac damage compared with continuous aortic cross-clamping. The converse is implied, in that the anoxic heart may benefit from the physiological effects of briefly reperfused oxygenated blood.     

Myocardial reactive hyperemia caused by initial myocardial anoxia during aortic valve replacement

Reactive hyperemic response of individual coronary arteries and of the whole heart to anoxia during coronary cannulation was investigated in 10 patients undergoing aortic valve replacement. Reactive hyperemic response in man is identical to that reported in experimental investigations. The duration of hyperemic response was dependent on the length of the preceding period of anoxia; the longer the period of anoxia, the more prolonged was the hyperemic response. No significant collateral circulation between the coronary arteries could be demonstrated during prolonged anoxia of an individual coronary artery. Blood flow debt was almost always overpaid, but the repayment percentage decreased with the lengthening of the anoxic period, being 460 percent after a short period of anoxia (less than or equal to 2 minutes), 230 percent after an anoxic period of moderate length (3 to 5 minutes), and only 160 percent after a long period of anoxia (greater than or equal to 7 minutes). The total mean repayment of blood flow debt of the whole heart was 195 percent.     

Myocardial protection by retrograde cardioplegic perfusion through the right atrium

Three types of cardioplegic delivery with ink into the isolated canine hearts were compared: (1) antegrade aortic root perfusion (AARP), (2) retrograde coronary sinus perfusion (RCSP) and (3) retrograde right atrium perfusion (RRAP). Ink was not distributed in the area distal to the coronary occlusion by AARP but well distribution in the same area by RCSP or RRAP. The right ventricular wall and ventricular septum were poorly perfused by RCSP but well perfused by RRAP. During cardiopulmonary bypass, RRAP created a fairly rapid cardiac arrest and satisfactory myocardial cooling. During Perfusion, the right heart was somewhat dilated but all the 10 canine hearts rebeat well. The left and right ventricular ejection fraction showed no significant change after bypass. No marked myocardial ultrastructural injury was found in left and right ventricles at the end of 90 minutes' ischemia. 4 patient, 1 of whom had 162 minutes' aortic cross-clamping received RRAP in operations on ascending aorta or coronary arteries and the myocardial protect ion was satisfactory. No complication was found pertaining to RRAP.     

间断缺血心停搏在冠脉搭桥术中的应用

１９９２～１９９３年间为１８０例冠脉病变的病人施行冠脉搭桥术，全部病人均采用核甙抑制剂利多氟嗪预处理和低温（２８℃）间断缺血心停搏进行术中心肌保护。平均每例病人作冠状动脉端吻合３～４个，每个吻合口用９分钟，主动脉阻断累加时间约２５分钟，体外循环时间９０分钟，术后医院死亡率１．６％（３／１８０），无术后心梗发生。作者认为，冠脉搭桥术的术中心肌保护可采用核甙抑制剂和间断缺血心停搏方法，而不用心肌停搏液。     

Correlation of Patterns of Subendocardial Reperfusion and Left Ventricular Performance after Ischemia

Ninety-three dogs were studied with normothermic or hypothermic ischemia for 60 or 90 minutes, with or without potassium cardioplegia. Radioactive-labeled microspheres (9 ± 1) were injected into the aortic perfusion cannula just prior to aortic cross-clamping and at 2, 6, and 10 minutes after the clamp was released. Left ventricular (LV) function was analyzed with a right heart bypass model before and 45 minutes after the ischemia period. Changes in LV function were defined as the arithmetic difference in the center of mass between preischemia and postischemia computer-drawn Sarnoff curves.Regardless of technique of myocardial protection, increased subendocardial flow 2 minutes after ischemia correlated strongly with preservation of LV function (p < 0.01). Well-preserved hearts showed a rapid return to normal levels of coronary blood flow (p < 0.01). In contrast, a delay in the peaking of subendocardial flow to 10 minutes was associated with poor function (p < 0.01). There was a high correlation between ultrastructural morphology and LV function. While well-preserved hearts show early preferential subendocardial perfusion, the poorly protected myocardium is unable to restore adequate subendocardial flow early in the reperfusion period.     

Cariporide对未成熟兔心肌缺血再灌注损伤的保护作用

目的　探讨甲磺酸苯甲酰胍类化合物Cariporide对未成熟兔心肌缺血再灌注损伤的保护作用及其机制。　方法　以离体灌注幼兔心脏为模型 ,将 2 4只幼兔心脏随机均分为对照组 (应用St.ThomasⅡ液 )和实验组 (应用Cariporide St .ThomasⅡ液 ) ,常温缺血 60min ,期间每 2 0min灌注 1次保护液 ,恢复灌注后 ,测定心率、心律、平均动脉压、冠脉流量、左心室收缩压、左心室舒张末压、左心室压力微分 (±dp/dt)和心肌酶。将另 6只幼兔的心肌单细胞悬液随机均分为基础 (未予缺氧处理 )、钙对照和钙实验组 (经缺氧、再复氧处理 ,钙实验组于缺氧时加入Cariporide 1μmol/L) ,用激光共聚焦显微镜测定心肌细胞内游离钙 ([Ca2 ]i)浓度 ,以钙荧光强度比值表示。　结果　与对照组相比 ,实验组缺血、再灌注后室颤发生率低 ,心肌酶漏出量少 ,平均动脉压、左心室收缩压、冠脉流量及±dp/dt均明显增加 ,左心室舒张压低。未成熟兔心肌细胞内 [Ca2 ]i浓度 ,钙实验组比钙对照组明显减少 (P <0 0 1) ,钙实验组与基础组差异无显著意义 (14 4 6± 12 8与 13 75± 10 2 ,P >0 0 5)。结论　Cariporide对未成熟心肌缺血再灌注损伤有保护作用 ,其机制是抑制心肌细胞内 [Ca2 ]i超载引起的缺血再灌注损伤     

Effect of initial reperfusion temperature on myocardial preservation

The effect of initial postischemic reperfusion temperature on myocardial preservation was studied in the isolated working rat heart model. After baseline measurement of aortic flow rate, coronary flow rate, and heart rate, 40 hearts were subjected to 60 minutes of ischemic arrest at 15 degrees C induced with a single dose of cold potassium cardioplegic solution. Hearts were then revived with a 10 minute period of nonworking reperfusion at 28 degrees, 31 degrees, 34 degrees, or 37 degrees C (10 hearts each), followed by 5 minutes of nonworking reperfusion at normothermia, followed by 30 minutes of working perfusion. Repeat measurements of function were obtained and postischemic release of creatine kinase into coronary effluent was determined. Recovery of aortic flow was significantly reduced at lower initial reperfusion temperatures (75% at 28 degrees C versus 88% at 37 degrees C) and the effect was approximately linear throughout the range studied (p less than 0.05). Release of creatine kinase into coronary effluent was greater at lower initial reperfusion temperatures (421 ImU/min/gm wet weight at 28 degrees C versus 115 ImU/min/gm wet weight at 37 degrees C), also in a linear manner (p less than 0.05). In this model, initial postischemic hypothermic reperfusion is deleterious to cellular integrity and functional recovery of the preserved myocardium. Studies in higher animals and humans are warranted to further evaluate the effect of initial reperfusion temperature on myocardial preservation.     

Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion

To investigate whether retrograde continuous low-pressure perfusion of the coronary sinus could deliver cardioplegic solutions with oxygen and substrate beyond stenoses and result in improved myocardial preservation, we subjected 41 canine hearts to 90 minutes of ischemia with an occlusion on the circumflex coronary artery. There were four groups: Group I, antegrade (aortic root) crystalloid cardioplegia every 30 minutes during ischemia; Group II, antegrade plus topical cooling; Group III, continuous retrograde perfusion; Group IV, same as Group III, with an oxygenated perfluorocarbon. All solutions had a PO2 of 400 to 500 mm Hg. Intramyocardial oxygen and carbon dioxide tensions (PO2 and PCO2) and mean myocardial temperatures were monitored during ischemia, and left ventricular (LV) function was assessed before ischemia and after reperfusion. After global ischemia, the circumflex occlusion was released and the hearts reperfused. Following 60 minutes of reperfusion, isovolumic developed pressure returned to 36% +/- 4% and 41% +/- 5% of preischemic levels, respectively, in Groups I and II. By contrast, Groups III and IV (retrograde perfusion) had a significantly greater percent of recovery (78% +/- 5% and 73% +/- 5%). Circumflex area intramyocardial PO2 fell 20 and 25 mm Hg below preischemic levels in Groups I and II during ischemia, whereas in Group III, intramyocardial PO2 in the circumflex region remained near preischemic levels, and in Group IV, it rose 19 mm Hg. Mean myocardial temperature during ischemia in the circumflex area was significantly higher in Group I than in Groups II, III, and IV. Peak intramyocardial PCO2 in the circumflex region was significantly less in the retrogradely perfused hearts. Retrograde coronary sinus perfusion resulted in significant improvement in recovery of LV function, uniform myocardial cooling, normal intramyocardial PO2, and less intramyocardial PCO2 accumulation, despite the presence of a total circumflex coronary artery occlusion.     

Effect of noncoronary blood flow upon myocardial mitochondrial function during hypothermic anoxic arrest

Mongrel dogs (23) were subjected to the experimental study characterizing the effect of noncoronary blood flow upon myocardial mitochondrial respiration. Anoxic arrest for 60 minutes was obtained by cross-clamping of the aorta under hypothermic cardiopulmonary bypass, and heart was reperfused for 10 minutes, then heart was excised to obtain the endocardium, epicardium of the left ventricle and ventricular septum for study of mitochondrial function and myocardial blood flow. Myocardial blood flow was measured with carbonized plastic tracer⁴⁶Sc during cross-clamping of the aorta. Noncoronary blood flow showed equal distribution in the left ventricle and septum with flow of 0.16±0.23 ml/min/100g (endocardium). Mitochondrial respiratory function following 60 minutes of hypothermic anoxic arrest at 20°C recovered to normal level, and also no correlation was demonstrated between noncoronary blood flow during cross-clamping of the aorta and mitochondrial respiratory function. It was concluded that noncoronary blood flow was negligible with respect to the oxygen demand at 20°C of myocardial temperature, and that noncoronary blood flow during cross-clamping of the aorta was not correlated to mitochondrial protection from ischemia.     

Ultrastructural integrity of human ventricular myocardium following cardioplegic arrest.

The appearance of the ventricular myocardium in 6 patients electing coronary bypass operation was evaluated by electron microscope before and after aortic cross-clamping. Bypassing protocol included the induction of hypothermic cardioplegia by intermittent aortic root perfusion, with potassium chloride added to cold blood serving as the cardioplegic agent. Cross-clamp intervals ranged from 66 to 125 minutes. Ultrastructural alterations following bypass manipulations, and distinct from those observed before cross-clamping, were limited to the presence of extensive myocardiocytic pooling of glycogen. Scrutiny of the intramyocardial capillary bed following perfusion with the cardioplegic solution revealed no abnormalities attributable to, or intensified by, the bypass maneuver. These findings indicate that hypothermic potassium cardioplegia, as specified, is not injurious to human myocardial ultrastructure.