Myocardial metabolism during aortic valve replacement. II. Bolus infusion of cold blood for cardioplegia

Myocardial energy metabolism during hypothermic potassium cardioplegia with blood as the cardioplegia vehicle, given in one or two bolus doses, was studied in eight patients undergoing aortic valve replacement. Myocardial biopsies were taken from the left ventricle 10 min after aortic cross-clamping (a.c.) and immediately before declamping (d.c.) and were analyzed for ATP, creatine phosphate (CP), creatine (C) and lactate. The interindividual range of myocardial temperature was 11-19 degrees C at 10 min a.c. and 11-25 degrees C immediately before d.c. The myocardial ATP concentration fell (17.2 +/- 5.7-12.8 +/- 2.8 mmol X kg-1 dry muscle), the lactate concentration rose (64.7 +/- 35.8-136 +/- 33.8 mmol X kg-1 d.m.) and the total creatine pool (CP + C) was unchanged. Hypothermic blood cardioplegia conferred fairly good initial protection of the myocardium, but the reduction in ATP and the great lactate accumulation towards the end of cardioplegia, especially in patients with myocardial temperature reaching 19-25 degrees C, indicates that such protection is adequate only if the myocardial temperature is maintained between 11 and 18 degrees C.     

Myocardial metabolism during aortic valve replacement. I. Hypothermic crystalloid cardioplegia with mannitol

Myocardial energy metabolism during hypothermic potassium cardioplegia with addition of mannitol was studied in five patients undergoing aortic valve replacement. Myocardial biopsies were taken from the left ventricle 10 min after the aortic cross-clamping and immediately before declamping and were analyzed for ATP, lactate and glycogen. The ATP concentration fell (13.2 +/- 3.6-11.0 +/- 4.3 mmol X kg-1 dry muscle), the lactate concentration rose (61.5 +/- 17.6-86.6 +/- 13.3) and glycogen decreased (181 +/- 54-143 +/- 3 mmol X kg-1 d.m.). Use of mannitol in a crystalloid cardioplegia solution does not prevent pronounced anaerobic metabolism in the myocardium during aortic valve replacement.     

Clinical study of blood cardioplegia--for aerobic metabolism during aortic cross-clamping

Blood cardioplegia is considered to be superior in oxygenating potential, buffering potential, oncotic, and other physiologic effects. In clinical cases, however, it is unproven whether aerobic metabolism can be obtained by using blood cardioplegia during aortic cross-clamping. Aerobic metabolism during aortic cross-clamping was therefore evaluated in patients with valvular heart disease who underwent relatively long periods of ischemic arrest. Myocardial metabolism of oxygen, lactate and pyruvate was studied in 14 patients under 126 +/- 41.2 min of cardiac arrest, and intramyocardial carbon dioxide tension (PmCO2) was also monitored continuously in 23 patients who received 121 +/- 29.8 min of aortic cross-clamping. After aortic cross-clamping, 4 degrees C St. Thomas solution was infused for immediate cooling, followed by blood cardioplegia for replenishment every 20-25 min. Blood cardioplegia and myocardial temperature were maintained within 15-20 degrees C by using an automatic cardiac hypothermia control system. Myocardial oxygen extraction during the pre-ischemic period was 26.8 +/- 13.3%. At 15 and 30 min after reperfusion, it was 30.0 +/- 10.8% and 33.8 +/- 8.2%, respectively. During ischemic arrest, myocardial oxygen extraction decreased, but the infusion of blood cardioplegia kept it above 14.0 +/- 9.3% at all times. As for lactate metabolism, although some cases showed lactate production even before the aortic cross-clamping, lactate extraction was attained in some cases during blood cardioplegia perfusion. Changes in excess lactate and redox potential of lactate and pyruvate (delta Eh) showed that aerobic metabolism could be obtained in 13/32 (41%) infusions of blood cardioplegia. PmCO2 at the aortic cross-clamp was 47.0 +/- 27.7 mmHg, and gradually rose during the ischemic arrest, but only as far as 68.4 +/- 64.8 mmHg at the time of cross-clamp release. PmCO2 decreased with each infusion of blood cardioplegia, and the decrease lasted up to 10 minutes. Though PmCO2 began to rise thereafter, the effect of blood cardioplegia continued as long as 20-25 min after the infusion. In conclusion, blood cardioplegia provides aerobic metabolism during aortic cross-clamping even in clinical setting, provided that cardiac hypothermia and delivery of cardioplegic solution are maintained appropriately.     

Myocardial Protection During Aortic Valve Replacement: Cardiac Metabolism and Enzyme Release Following Continuous Blood Cardioplegia

Cardiac metabolism following hypothermic potassium cardioplegia with blood as cardioplegia vehicle was studied in two groups of patients undergoing aortic valve replacement. In 15 patients, blood was given as single dose infusion (single dose group) and in 18 patients the same initial bolus was followed by a continuous perfusion (25–30 ml/min) with modified blood from the heart-lung machine (continuous blood group). Simultaneous samples were drawn from arterial and coronary sinus blood before and during the first 60 min after cardioplegia. In the continuous blood group, samples were also drawn during the period of cardiopiegic perfusion. The samples were analysed for PO₂, O₂-saturation and content, PCO₂, pH, lactate, pyruvate, glucose, potassium, myoglobin, creatine kinase (CK), its isoenzyme MB, and aspartate aminotransferase (ASAT). In addition myoglobin and enzymes were followed in peripheral venous blood for 24 hours. Myocardial biopsies were taken from the left ventricle at the beginning and end of cardioplegia and analyzed for adenosine triphosphate (ATP), creatine (C) and cieatinephosphate (CP). The pattern of metabolic changes after cardioplegia was similar in both groups with decreased myocardial oxygen extraction, marked lactate and potassium release, increased glucose uptake and significant enzyme and myoglobin release. However, the degree of changes was significantly smaller in the continuous blood group. The myocardial biopsies also showed significantly less ATP and CP decrease in the continuous blood group, suggesting, together with the other metabolic results, that the myocardial protection afforded by continuous blood cardioplegia was superior to that of the single dose group. Furthermore, continuous perfusion permitted easy control of myocardial temperature during the period of aortic cross-clamping.     

Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery?

OBJECTIVE: Intermittent antegrade blood cardioplegia (IABC) has been standardized as a routine technique for myocardial protection in coronary surgery. However, if the myocardium is known to tolerate short periods of ischemia during hypothermic arrest, it may be less tolerant of warm ischemia, so the optimal cardioplegic temperature of intermittent antegrade blood cardioplegia is still controversial. The aim of this study was to compare the effects of warm intermittent antegrade blood cardioplegia and cold intermittent antegrade blood cardioplegia on myocardial pH and different parameters of the myocardial metabolism. METHODS: Thirty patients undergoing first-time isolated coronary surgery were randomly allocated into two groups: group 1 (15 patients) received warm (37 degrees C) intermittent antegrade blood cardioplegia and group 2 (15 patients) received cold (4 degrees C) intermittent antegrade blood cardioplegia. The two randomization groups had similar demographic and angiographic characteristics. Total duration of cardiopulmonary bypass (108+/-17 and 98+/-21 min) and of aortic cross-clamping (70+/-13 and 65+/-15 min) were similar. The cardioplegic solutions were prepared by mixing blood with potassium and infused at a flow rate of 250 ml/min for a concentration of 20 mEq/l during 2 min after each anastomosis or after 15 min of ischemia. Intramyocardial pH was continuously measured during cardioplegic arrest by a miniature glass electrode and values were corrected by temperature. Myocardial metabolism was assessed before aortic clamping (pre-XCL), 1 min after removal of the clamp (XCL off) and 15 min after reperfusion (Rep) by collecting coronary sinus blood samples. All samples were analyzed for lactate, creatine kinase (MB fraction), myoglobin and troponin I. Creatine kinase and troponin I were also daily evaluated in peripheral blood during 6 days post-operatively. RESULTs: The clinical outcomes and the haemodynamic parameters between the two groups were identical. In group 1, XCL off and Rep were associated with higher coronary sinus release of lactate (5.5 +/- 1.8 and 2.2 +/- 0.5 mmol/l) than in group 2 (2.0 +/- 0.7 and 1.6 +/- 0.3 mmol/l, P < 0.05). Mean intramyocardial pH was lower in group 1 (7.23 +/- 0.08) than in group 2 (7.65 +/- 0.30, P < 0.05). There were no significant differences between the two groups with respect of creatine kinase (MB fraction) either after Rep or during the post-operative period. Lower coronary sinus release of myoglobin was detected at Rep in group 1 (170 +/- 53 microg/l) than in group 2 (240 +/- 95 microg/l, P < 0.05). At day 1, a lower release of troponin I was found in group 1 (0.11 +/- 0.07 g/ml) compared to group 2 (0.17 +/- 0.07 ng/ml, P < 0.05). CONCLUSION: With regards to similar clinical and haemodynamic results, myocardial protection induced by warm IAEX is associated with more acidic conditions (intramyocardial pH and lactate release) and less myocardial injury (myoglobin and troponin I release) than cold intermittent antegrade blood cardioplegia during coronary surgery.     

Myocardial energy depletion during profound hypothermic cardioplegia for cardiac operations

Myocardial biopsy specimens were taken from 10 patients undergoing aortic valve replacement using extracorporeal circulation and continuous perfusion blood cardioplegia at extremely low myocardial temperature (10 degrees C). They were analyzed for adenosine triphosphate, creatine phosphate, creatine, and lactate before, after 10 minutes, and after 60 minutes of cardioplegia. Patient inclusion criteria were heart volume less than 700 ml/m2 body surface area and no significant coronary atherosclerosis as judged from preoperative angiograms. The profound hypothermic cardioplegia resulted in a smaller intramyocardial lactate accumulation but a greater decrease in adenosine triphosphate and creatine phosphate than a moderate reduction of myocardial temperature (15 degrees C) as previously reported in a similar patient group. This suggests that at the lower temperature energy-generating processes are thwarted more than energy consumption. In addition, the profound hypothermic cardioplegia led to a reduction of the myocardial pool of total creatine, which may delay restitution of myocardial high-energy phosphate and function after cardioplegia.     

Right and left ventricular metabolites

Current methods of cardioplegic delivery may delay the recovery of right ventricular metabolism and function. To evaluate right and left ventricular metabolism, we performed biopsies in 37 patients undergoing elective coronary bypass operation with aortic root blood cardioplegia. Right ventricular temperatures were warmer than left ventricular temperatures during cardioplegic arrest (right ventricle: 16.8 degrees +/- 3.8 degrees C, left ventricle: 14.3 degrees +/- 3.7 degrees C, p = 0.02). Adenosine triphosphate concentrations were lower in the right ventricle than in the left ventricle before cardioplegic arrest (right ventricle: 13.8 +/- 7.8 mmol/kg, left ventricle: 21.5 +/- 8.7 mmol/kg, p = 0.02). After reperfusion, right ventricular adenosine triphosphate concentrations fell to low levels (10 +/- 6 mmol/kg). Postoperative left and right ventricular high energy phosphate concentrations (the sum of adenosine triphosphate and creatine phosphate levels) correlated inversely with myocardial temperatures during cardioplegia (r = -0.29, p = 0.048). Aortic root cardioplegia did not cool the right ventricle as well as it did the left ventricle. The lower preoperative high energy phosphate concentrations may have increased the susceptibility of the right ventricle to ischemic injury. Alternative methods of myocardial preservation may improve right ventricular cooling and protection.     

Atrial activity during cardioplegia and postoperative arrhythmias

Cardioplegia provides excellent protection for the left ventricle, but the right atrium may be poorly protected. Myocardial temperatures, right atrial electrical activity, and postoperative arrhythmias were assessed in 103 patients participating in two consecutive randomized trials comparing blood cardioplegia (n = 36), crystalloid cardioplegia (n = 38), and diltiazem crystalloid cardioplegia (n = 29). Both right atrial and right ventricular temperatures were significantly warmer (p less than 0.05) during delivery of the blood cardioplegic solution than during delivery of either the crystalloid or the diltiazem crystalloid cardioplegic solutions; the aortic root temperatures were 9 degrees +/- 2 degrees C with blood cardioplegia and 5 degrees + 1 degrees C with both crystalloid and diltiazem crystalloid cardioplegia. Atrial activity during cardioplegic arrest was greatest with blood cardioplegia (12 +/- 3 beats/min), lower with crystalloid cardioplegia (10 +/- 2 beats/min), and minimal with diltiazem crystalloid cardioplegia (5 +/- 1 beats/min, p less than 0.05). Perioperative ischemic injury (by creatine kinase MB isoenzyme analysis) was greatest with crystalloid cardioplegia (p less than 0.05). Postoperative supraventricular arrhythmias (both treated and untreated) were more frequent after crystalloid cardioplegia (crystalloid, 63%; blood, 40%; diltiazem, 47%; p less than 0.05). Patients in whom supraventricular arrhythmias developed had significantly more postoperative ischemic injury (by creatinine kinase MB isoenzyme analysis, p less than 0.05). Blood cardioplegia reduced supraventricular arrhythmias by reducing ischemic injury despite warmer intraoperative temperatures and more right atrial activity. Diltiazem crystalloid cardioplegia reduced postoperative arrhythmias by improving intraoperative myocardial protection and suppressing intraoperative and postoperative atrial activity. Crystalloid cardioplegia cooled but did not arrest the right atrium intraoperatively, resulted in the most perioperative ischemic injury, and yielded the highest incidence of postoperative supraventricular arrhythmias.     

Donor hearts with impaired hemodynamics. Benefit of warm substrate-enriched blood cardioplegic solution for induction of cardioplegia during cardiac harvesting.

Brain-dead donors frequently show circulatory deterioration and often require so much inotropic support that the donor heart is of questionable value. This experimental study quantifies the cardiac metabolic consequences of brain death and the role of warm blood cardioplegic solution for induction of cardioplegia to improve the quality of potential donor hearts with impaired hemodynamics. Twelve dogs were subjected to brain death by interrupting cerebral blood flow (ligation of innominate artery, carotid arteries, and superior vena cava) and were followed up for as long as 6 hours. Each showed progressive hemodynamic deterioration, necessitating inotropic support (dopamine, calcium, and epinephrine) and large amounts of volume replacement (hetastarch; Hespan) to support the circulation (maintain mean arterial blood pressure greater than 60 mm Hg). Biopsy specimens were taken after 6 hours, or when irreversible ventricular fibrillation occurred, and were analyzed for adenosine triphosphate, creatine phosphate, glycogen, glutamate, and lactate. In six dogs the aorta was then clamped, and a 10-minute infusion of warm (37 degrees C) substrate-enriched aspartate/glutamate blood cardioplegic solution (with the dog's own blood) was given by roller pump to simulate warm induction during the harvesting process. Biopsies were then repeated. Myocardial metabolism, expressed as percent of control values, during brain death was characterized by the following: (1) moderate energy depletion (adenosine triphosphate fell 25% +/- 8%, creatine phosphate fell 55% +/- 15%; p less than 0.05 versus control: mean +/- standard error of the mean); (2) substrate depletion (tissue glutamate fell 48% +/- 9.5%, glycogen fell 66% +/- 7.5%; p less than 0.05 versus control: mean +/- standard error of the mean); and (3) evidence of anaerobic metabolism (lactate increased 374% +/- 95%; p less than 0.05 versus control: mean +/- standard error of the mean). Warm induction of blood cardioplegia in these energy- and substrate-depleted ischemic hearts showed (1) return of creatine phosphate levels to normal (113% +/- 16.8%), (2) replenishment of glutamate (201% +/- 24% of control; p less than 0.05 versus control: mean +/- standard error of the mean), and (3) 43% +/- 14% reduction in myocardial lactate content; (p less than 0.05 versus brain-dead animals). These data suggest that brain-dead donors requiring inotropic support sustain energy and substrate depletion and ischemic damage that can be reversed by a brief period of induction of cardioplegia with a warm substrate-enriched blood cardioplegic solution before harvesting.(ABSTRACT TRUNCATED AT 400 WORDS)     

A biochemical and ultrastructural study on myocardial changes during aorto-coronary bypass surgery: St. Thomas Hospital cardioplegia versus intermittent aortic cross-clamping at 34 and 25 degrees C

The changes induced by continuous aortic cross-clamping in combination with multidose ice-cold St. Thomas Hospital cardioplegia (myocardial temperature below 16 degrees C), or intermittent aortic cross-clamping at 34 or 25 degrees C were evaluated in a randomized study on 72 patients undergoing extensive aorto-coronary bypass surgery. The cumulative release of heart-specific enzymes was very small and no marked ultrastructural changes in mitochondria of both the subepi- and the subendocardial layer of the left ventricular free wall occurred. No differences between the three operation techniques could be observed on the basis of the above-mentioned parameters. Myocardial ATP and glycogen contents were decreased in post-ischaemic tissue in both the normothermic and hypothermic intermittent aortic cross-clamp groups. This decrease was associated with a release of lactate and inorganic phosphate during the repetitive periods of reperfusion. No change in myocardial ATP and glycogen content could be observed in the cardioplegia-treated hearts. St. Thomas Hospital cardioplegia is obviously most effective in preventing changes in myocardial metabolism such as reduction of ATP and carbohydrate stores during the reversible phase of ischaemic insult.     

Cold blood as the vehicle for potassium cardioplegia

Cold blood with potassium, 34 mEq/L, was compared with cold blood and with a cardioplegic solution. Three groups of 6 dogs had 2 hours of aortic cross-clamp while on total bypass at 28 degrees C with the left ventricle vented. An initial 5-minute coronary perfusion was followed by 2 minutes of perfusion every 15 minutes for the cardioplegic solution (8 degrees C) and every 30 minutes for 3 minutes with cold blood or cold blood with potassium (8 degrees C). Hearts receiving cold blood or cold blood with potassium had topical cardiac hypothermia with crushed ice. Peak systolic pressure, rate of rise of left ventricular pressure, maximum velocity of the contractile element, pressure volume curves, coronary flow, coronary flow distribution, and myocardial uptake of oxygen, lactate, and pyruvate were measured prior to ischemia and 30 minutes after restoration of coronary flow. Myocardial creatine phosphate (CP), adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were determined at the end of ischemia and after recovery. Changes in coronary flow, coronary flow distribution, and myocardial uptake of oxygen and pyruvate were not significant. Peak systolic pressure and lactate uptake declined significantly for hearts perfused with cold blood but not those with cold blood with potassium. ATP and ADP were lowest in hearts perfused with cardioplegic solution, and CP and ATP did not return to control in any group. Heart water increased with the use of cold blood and cardioplegic solution. Myocardial protection with cold blood with potassium and topical hypothermia has some advantages over cold blood and cardioplegic solution.     

Metabolic evidence that regional hypothermia induced by cold saline protects the heart during ischemic arrest

The rationale for cold saline induced hypothermic myocardial protection during ischemic cardioplegia has been limited for the most part to empiric and contractility observations. The aim of this study was to evaluate the degree of metabolic protection afforded by this procedure. In 21 dogs (C) placed on total cardiopulmonary bypass, normothermic ischemic arrest was induced for 60 min followed by 30 min of reperfusion. In 8 other dogs (CS), similarly treated, the heart was continuously cooled with saline at 5°C before and during the ischemia. Myocardial biopsies analyzed for ATP, ADP, creatine phosphate (CP), lactate and glycogen (Gly), were obtained before cross clamping at 15, 30, 45 and 60 min of ischemia and after 30 min of reperfusion.Significantly higher levels of ATP, CP and Gly were found in the CS hearts during and following the cross clamp period. These data indicate that local hypothermia slows the breakdown of high energy phosphate moieties during ischemic arrest. However, despite the protection afforded, ATP remains significantly depressed following reperfusion.     

Myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using cold or warm blood cardioplegia.

OBJECTIVES: Myocardial protection techniques during cardiac surgery have been largely investigated in the clinical setting of coronary revascularisation. Few studies have been carried out on patients with left ventricular hypertrophy where the choice of delivery, and temperature of cardioplegia remain controversial. This study investigates metabolic changes and myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using antegrade cold or warm blood cardioplegia. METHODS: Thirty-five patients were prospectively randomised to intermittent antegrade cold or warm blood cardioplegia. Left ventricular biopsies were collected at 5min following institution of cardiopulmonary bypass, 30min after cross-clamping the aorta and 20min after cross-clamp removal, and used to determine metabolic changes during surgery. Metabolites (adenine nucleotides, amino acids and lactate) were measured using high pressure liquid chromatography and enzymatic techniques. Postoperative myocardial troponin I release was used as a marker of myocardial injury. RESULTS: Ischaemic arrest was associated with significant increase in lactate and alanine/glutamate ratio only in the warm blood group. During reperfusion, alanine/glutamate ratio was higher than preischaemic levels in both groups, but the extent of the increase was considerably greater in the warm blood group. Troponin I release was markedly (P<0.05, Mean+/-SD) lower at 1, 24 and 48h postoperatively in the cold compared to the warm blood group (0.51+/-0.37, 0.37+/-0.22 and 0.27+/-0.19 vs. 0.75+/-0.42, 0.73+/-0.51 and 0.54+/-0.38ng/ml for cold vs. warm group, respectively). CONCLUSIONS: Cold blood cardioplegia is associated with less ischaemic stress and myocardial injury compared to warm blood cardioplegia in patients with aortic stenosis undergoing valve replacement surgery. Both cardioplegic techniques, however, confer sub-optimal myocardial protection.     

Metabolic changes and myocardial injury during cardioplegia: a pilot study.

BACKGROUND: The timing, nature, and severity of both increased cardiac troponin I (cTn-I) levels and myocardial injury during ischemic arrest with cardioplegia are unknown. To define them more accurately, we studied myocardial metabolic activity and the release of markers of myocardial cell injury into the coronary sinus before, during, and after cardioplegia. METHODS: We simultaneously measured creatine kinase, creatine kinase-MB, cTn-I, lactate, phosphate, and blood gases in coronary sinus and systemic arterial blood from 12 patients before cardiopulmonary bypass, after removal of the aortic cross-clamp, and after discontinuation of cardiopulmonary bypass. We also measured coronary sinus flow and transmyocardial fluxes of all analytes and calculated myocardial oxygen consumption, myocardial carbon dioxide production, and myocardial energy expenditure. RESULTS: Myocardial lactate release increased 10-fold after removal of the aortic cross-clamp (p = 0.012) and was accompanied by a surge in myocardial phosphate uptake (p = 0.056). These events were associated with only partial cardioplegia-induced suppression of myocardial oxygen consumption (p = 0.0047), myocardial carbon dioxide production (p = 0.0022), and myocardial energy expenditure (p = 0.0029). Simultaneously, coronary sinus cTn-I levels increased from a mean of 0.76 to 2.43 ng/mL after removal of the aortic cross-clamp, and 2.51 ng/mL after cardiopulmonary bypass (p = 0.014), leading to an increase in arterial cTn-I concentration from 0.18 to 0.98 and 3.01 ng/mL (p = 0.0002). Thus, cTn-I release across the myocardium was absent at baseline, became detectable (p = 0.012) after removal of the aortic cross-clamp, and correlated with cross-clamp and pump times. Similar changes occurred with creatine kinase-MB. CONCLUSIONS: Metabolic myocardial stress occurs during ischemic arrest with cardioplegia and is associated with inadequate suppression of metabolism and with a surge in cTn-I and creatine kinase-MB release, which is maximal after removal of the aortic cross-clamp. These changes are likely to represent structural myocardial cell injury.     

Myocardial protection with Hamburg oxygenated crystalloid cardioplegic solution for multiple coronary bypass and multivalvular replacement

We evaluated myocardial protection with Hamburg oxygenated crystalloid cardioplegic solution in a double study. Part I was a prospective metabolic study, measuring myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) contents before and after ischemia in 30 coronary bypass (CABG) patients. During ischemia, CP levels decreased significantly, whereas ATP did not. After 10 minute of reperfusion, mean ATP contents were 90% of preischemic values and CP levels increased to 85% of preischemic values. Spontaneous myocardial defibrillation was seen in 93.3% of patients. Part II included evaluation of early postischemic myocardial function in 228 patients, 48 with multiple valve replacement (MUVR) and 180 with CABG. Spontaneous myocardial defibrillation was seen in 90.3%. Cardiac index, measured before and 1 and 12 hours after surgery, increased significantly in the postischemic period (from 1.95 +/- 0.9 to 2.5 +/- 0.7 l/min m2 in MUVR, p 0.04; from 2.2 +/- 0.6 to 2.7 +/- 0.7 l/min/m2 in CABG, p 0.01). Myocardial infarction frequency was 3% among CABG patients, and unrelated to the number of distal anastomosis or to aortic cross-clamp time. Early postoperative mortality was 6.2% for MUVR and 0.5% for CABG. Thus, oxygenated cardioplegia with Hamburg solution preserves high-energy phosphate compounds and prevents ischemic injury, with excellent short-term clinical results.     

Enhanced myocardial protection with high-energy phosphates in St. Thomas' Hospital cardioplegic solution. Synergism of adenosine triphosphate and creatine phosphate

The potential for improving myocardial protection with the high-energy phosphates adenosine triphosphate and creatine phosphate was evaluated by adding them to the St. Thomas' Hospital cardioplegic solution in the isolated, working rat heart model of cardiopulmonary bypass and ischemic arrest. Dose-response studies with an adenosine triphosphate range of 0.05 to 10.0 mmol/L showed 0.1 mmol/L to be the optimal concentration for recovery of aortic flow and cardiac output after 40 minutes of normothermic (37 degrees C) ischemic arrest (from 24.1% +/- 4.4% and 35.9% +/- 4.1% in the unmodified cardioplegia group to 62.6% +/- 4.7% and 71.0% +/- 3.0%, respectively, p less than 0.001). Adenosine triphosphate at its optimal concentration (0.1 mmol/L) also reduced creatine kinase leakage by 39% (p less than 0.001). Postischemic arrhythmias were also significantly reduced, which obviated the need for electrical defibrillation and reduced the time to return of regular rhythm from 7.9 +/- 2.0 minutes in the control group to 3.5 +/- 0.4 minutes in the adenosine triphosphate group. Under more clinically relevant conditions of hypothermic ischemia (20 degrees C, 270 minutes) with multidose (every 30 minutes) cardioplegia, adenosine triphosphate addition improved postischemic recovery of aortic flow and cardiac output from control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 58.0% +/- 4.7% and 64.4% +/- 3.7% (p less than 0.01), respectively, and creatine kinase leakage was significantly reduced. Parallel hypothermic ischemia studies (270 minutes, 20 degrees C) using the previously demonstrated optimal creatinine phosphate concentration (10.0 mmol/L) gave nearly identical improvements in recovery and enzyme leakage. The combination of the optimal concentrations of adenosine triphosphate and creatine phosphate resulted in even greater myocardial protection; aortic flow and cardiac output improved from their control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 79.7% +/- 1.1 and 80.7% +/- 1.0% (p less than 0.001), respectively. In conclusion, both extracellular adenosine triphosphate and creatine phosphate alone markedly improve the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution during prolonged hypothermic ischemic arrest, but together they act additively to provide even greater protection.     

Myocardial protection during aortic valve replacement. effects of mannitol in the cardioplegic solution on cardiac metabolism and enzyme release

Myocardial substrate metabolism and enzyme release following hypothermic potassium cardioplegia with and without the addition of mannitol in the cardioplegic solution were studied in two series of patients undergoing isolated aortic valve replacement. Measurements were made of PO2. O2-saturation and content, PCO2, pH, glucose, lactate, pyruvate, potassium, myoglobin, creatine kinase (CK), its isoenzyme MB and aspartate aminotransferase (ASAT) simultaneously in arterial and coronary sinus blood before cardioplegia and during the first 60 min after the release of aortic cross-clamping. In addition, myoglobin and enzymes were followed in peripheral venous blood for 72 hours after cardioplegia. Analysis of the results revealed no striking difference between the groups. Nevertheless, with the addition of mannitol, there was a slightly lower release of lactate and myoglobin probably indicating a more rapid metabolic recovery of the myocardium.     

Insulin(GIK) improves myocardial metabolism in patients during blood cardioplegia

The aim of this study was to test the hypothesis that abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion are attenuated further by insulin(GIK) than by alpha-ketoglutarate enrichment of blood cardioplegia alone. Twenty-eight males (47 to 78 years) undergoing coronary artery bypass grafting (CABG) participated in a prospective, controlled, randomized study. All patients had alpha-ketoglutarate-enriched blood cardioplegia. Insulin(GIK) was infused in 13 patients during aortic cross-clamping. Insulin(GIK) prevented lactate release during cardioplegia (1.5+/-15 vs -44+/-14 micromol/min, p = 0.04), and a significant extraction of lactate was induced shortly after declamping the aorta (15+/-3 vs 2+/-1%, p = 0.001). Free fatty acid uptake was reduced after cardioplegic cross-clamping (5.7+/-1.6 vs 16.0+/-3.8 micromol/min, p = 0.02). More positive/less negative levels of alanine, aspartate, glutamine, glycine, ornithine, taurine and tyrosine were found in all the insulin-treated patients. We conclude that insulin(GIK) attenuates abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion further than is obtained with alpha-ketoglutarate enrichment of blood cardioplegia alone.     

Diltiazem cardioplegia. A balance of risk and benefit

Calcium channel blockers may prevent myocardial injury during cardioplegia and reperfusion. A prospective, randomized trial was instituted to evaluate the hemodynamic and myocardial metabolic recovery in 40 patients undergoing elective aorta-coronary bypass with either diltiazem in crystalloid potassium cardioplegia (n = 20) or crystalloid potassium cardioplegia (n = 20). In a preliminary trial, doses between 150 and 250 micrograms/kg reduced the period of heart block after cross-clamp removal (90 +/- 110 minutes) from that found with higher doses and improved myocardial metabolism. In the randomized trial, diltiazem cardioplegia (150 micrograms/kg) produced coronary vasodilatation during cardioplegia and produced less reactive hyperemia during reperfusion. Myocardial oxygen extraction was lower and myocardial lactate production was less after diltiazem cardioplegia during reperfusion. Tissue adenosine triphosphate and creatine phosphate concentrations were preserved better after diltiazem cardioplegia. The postoperative creatine kinase MB levels were less (p less than 0.05) after diltiazem cardioplegia, which indicated less myocardial injury. Postoperative volume loading demonstrated that systolic function (the relation between systolic blood pressure and end-systolic volume index) was depressed after diltiazem cardioplegia compared to crystalloid cardioplegia, but cardiac index was higher because afterload (mean arterial pressure) was lower and preload (end-diastolic volume index) was higher. Diltiazem cardioplegia preserved high-energy phosphates, improved postoperative myocardial metabolism, and reduced ischemic injury after elective coronary bypass. However, diltiazem was a potent negative inotrope and produced prolonged periods of electromechanical arrest. Diltiazem cardioplegia may be of value in patients with severe ischemia but should be used with caution in patients with ventricular dysfunction, and a dose-response relation must be established at each institution before clinical use.     

Evaluation of myocardial preservation using 31P NMR

The purpose of this study was (1) to monitor myocardial high-energy phosphate content and recovery of left ventricular (LV) contractile function following normothermic graded cardiac ischemia and single-dose hypothermic potassium cardioplegia, and (2) to assess the temporal limits of LV functional recovery during single-dose cardioplegia maintained at 17 degrees C. Rabbit hearts (30) were perfused, equipped with an LV balloon, paced at 240 beats/min, and placed in a nuclear magnetic resonance (NMR) magnet. Hearts underwent either graded, global normothermic ischemia or potassium cardioplegia arrest maintained at 17 degrees C for 1 hr. Myocardial high-energy phosphate level, LV contractility, and temperature were monitored continuously. Phosphocreatine (PCr) fell to 10 +/- 2, 2 +/- 1, and 0% of control and ATP to 70 +/- 3, 19 +/- 7, and 0% of control at 10, 40, and 60 min of 37 degrees C ischemia. After 1 hr of reperfusion, regression analysis of final developed pressure (DP) on end ischemic ATP (EIATP) content revealed: DP = 1.02 EIATP + 18 (r = 0.95). Following single-dose cardioplegia, maintained at 17 degrees C, PCr fell to 16 +/- 3% of control at 60 min while ATP fell only to 92 +/- 5% control. With reperfusion, recovery of DP was 100%. It was concluded that (1) PCr serves as an energy buffer for ATP, (2) EIATP predicts recovery of LV function, (3) single-dose cardioplegia maintained at 17 degrees C provides complete myocardial preservation for up to 60 min.