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The myocardial recovery mode after cold storage for transplantation with Collins' solution and cardioplegic solution. A functional and metabolic study in the rat heart.

Mechanisms and kinetics of the effects of the ionic composition of two different storage solutions, an intracellular type and an extracellular type, were analyzed by examining the myocardial functional and metabolic recovery processes during the early reperfusion periods after 3 hours of cold storage using an isolated perfused working rat heart model. The hearts were stored either in our own cardioplegic solution (group 1) or in Collins' solution (group 2) for 3 hours at 4 degrees C and were then reperfused. The electromechanical activity in group 1 was elevated, as indicated by a higher incidence of ventricular fibrillation at 5 minutes of reperfusion (group 1: 5/6; group 2: 0/5; p < 0.05). The coronary flow rate in group 2 was significantly lower, at least for the first 15 minutes after reperfusion, than that of group 1, suggesting the possible existence of vasoconstriction in group 2. Although myocardial oxygen uptake during this period was smaller in group 2, the recovery of myocardial high-energy phosphate levels was better and creatine kinase leakage was less in group 2. The recovery of aortic flow after 30 minutes of reperfusion was significantly better in group 2 (group 1, 59.1 +/- 5.8%; group 2, 71.7 +/- 6.0%; p < 0.01), although the early recovery was somewhat worse in group 2. These data suggest that the heart stored in an intracellular-type solution, compared with one stored in an extracellular-type solution, recovers in an electromechanically suppressed fashion during the early reperfusion phase, associated with a better metabolic recovery and a slower but larger functional recovery. The disadvantage of the intracellular-type solution, however, may be its effect on the increase of coronary vascular resistance during the early reperfusion period.

Animals↗

[Effects of cardioplegic solutions on coronary artery and myocardium--comparison of the glucose-insulin-potassium solution and the St. Thomas' Hospital cardioplegic solution].

Effects of two cardioplegic solutions on coronary artery and myocardium were experimentally investigated in three types of preparations. In the isolated perfused guinea pig heart, infusion of Glucose-Insulin-Potassium (GIK) solution (37 degrees C) caused contraction of coronary artery, whereas the St. Thomas' Hospital cardioplegic solution (37 degrees C) produced vasodilation. At the end of 30 minutes reperfusion after continuous infusion of cardioplegic solution, the St. Thomas' Hospital cardioplegic solution produced a greater recovery of cardiac function than GIK solution. In the isolated pig coronary artery, vasoconstriction caused by high potassium content was diminished by addition of magnesium in concentration dependent manner. In the electrophysiological examination, the membrane potential of the guinea pig papillary muscle was recorded by means of conventional glass microelectrodes. Though GIK solution produced greater depolarization of resting membrane potential than the St. Thomas' Hospital cardioplegic solution, effects of the two different cardioplegic solution was not so different after reperfusion of Tyrode solution. The St. Thomas' Hospital cardioplegic solution resulted in greater recovery of contracting activity after reperfusion than GIK solution. These data suggest that GIK solution causes coronary vasoconstriction and has deleterious effects on myocardium and that the St. Thomas' Hospital cardioplegic solution has a vasodilating action and produced a greater myocardial protection than GIK solution.

Animals↗

A clinical trial comparing University of Wisconsin solution and cold cardioplegic solution with load-independent mechanical parameters.

To evaluate the efficacy of University of Wisconsin solution for clinical heart transplantation, load-independent parameters were used to assess left ventricular function after transplantation. Donor hearts were arrested with and stored in buffered cold cardioplegic solution for control (n = 5) and University of Wisconsin solution for the experimental group (n = 5). Orthotopic transplantations were performed in a routine manner. Mean donor age (cardioplegic solution, 28 +/- 5.2 years; University of Wisconsin solution, 28 +/- 5.1 years) and ischemic times (cardioplegic solution, 181 +/- 27 minutes; University of Wisconsin solution, 224 +/- 23 minutes) were similar. Two hours after reperfusion of the heart, transesophageal echocardiography was used to image the left ventricle at the mid-papillary muscle level, and a high-fidelity catheter-tipped manometer was placed in the left ventricle to record left ventricular pressure simultaneously. These images were digitized during apneic baseline conditions and during an acute reduction in preload from inferior vena caval occlusion. The left ventricular cross-sectional areas were measured and matched with left ventricular pressure from the catheter-tipped manometer to reveal pressure-area relationships. The baseline parameters fractional area change and stroke force were calculated. End-systolic elastance, the slope of end-systolic pressure-area relationship and preload recruitable stroke force, the slope of stroke force versus end-diastolic area were calculated from the inferior vena cava occlusion measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Coronary sinus ostial occlusion during retrograde delivery of cardioplegic solution significantly improves cardioplegic distribution and efficacy.

UNLABELLED: This study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed. METHODS: Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow). RESULTS: Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 +/- 0.40 ml/gm versus 1.06 +/- 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% +/- 15.1% to 61.3% +/- 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex. CONCLUSION: Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered.

Capillaries↗

St. Thomas' Hospital cardioplegic solution. Beneficial effect of glucose and multidose reinfusions of cardioplegic solution.

The intention of this study was to determine whether glucose is beneficial in a cardioplegic solution when the end products of metabolism produced during the ischemic period are intermittently removed. The experimental model used was the isolated working rat heart, with a 3-hour hypothermic 10 degrees C cardioplegic arrest period. Cardioplegic solutions tested were the St. Thomas' Hospital No. 2 and a modified Krebs-Henseleit cardioplegic solution. Glucose (11 mmol/L) was beneficial when multidose cardioplegia was administered every 30 minutes. Including glucose in Krebs-Henseleit cardioplegic solution improved postischemic recovery of aortic output from 57.0% +/- 1.8% to 65.8% +/- 2.2%; p less than 0.025. The addition of glucose to St. Thomas' Hospital No. 2 cardioplegic solution improved aortic output from 74.6% +/- 1.9% to 87.4% +/- 1.9%; p less than 0.005. Furthermore, a dose-response curve showed that a glucose concentration of 20 mmol/L gave no better recovery than 0 mmol/L, and glucose in St. Thomas Hospital No. 2 cardioplegic solution was beneficial only in the range of 7 to 11 mmol/L. In addition, we showed that multidose cardioplegia was beneficial independent of glucose. Multidose St. Thomas' Hospital No. 2 cardioplegia, as opposed to single-dose cardioplegia, improved aortic output recovery from 57.4% +/- 5.2% to 74.6% +/- 1.9%; p less than 0.025, and with St. Thomas' Hospital No. 2 cardioplegic solution plus glucose (11 mmol/L) aortic output recovery improved from 65.9% +/- 2.9% to 87.4% +/- 1.9%; p less than 0.005. Hence, at least in this screening model, the St. Thomas' Hospital cardioplegic solution should contain glucose in the range of 7 mmol/L to 11 mmol/L, provided multidose cardioplegia is given. We cautiously suggest extrapolation to the human heart, on the basis of supporting clinical arguments that appear general enough to apply to both rat and human metabolisms.

Animals↗

Cardioplegia and vascular injury. Dissociation of the effects of ischemia from those of the cardioplegic solution.

Although cardioplegic solutions successfully protect myocardial contractile cells against ischemic injury, their effect on the vasculature remains controversial. To address this we used a vascular bed preparation (isolated rat mesentery) that permits the study of vascular function without the coincident changes in contractile status that affect vascular tone (and hence the assessment of vascular function in isolated hearts). Smooth muscle cell contraction was assessed by measurement of the vasoconstrictor response to phenylephrine, and relaxation was assessed by measurement of the vasodilator responses to sodium nitroprusside and the endothelium-dependent relaxant adenosine triphosphate. After characterization of basal vascular function, mesenteries were subjected to normothermic ischemia for 60, 90, 120, 150, and 180 minutes (n = 12 for each time period; 6 preparations were subjected to ischemia alone and 6 to ischemia preceded by a 3-minute infusion of the St. Thomas' Hospital cardioplegic solution). The tissue was then reperfused for 20 minutes and vascular function reassessed. Ischemia alone caused progressive time-dependent deterioration in vasoconstrictor responses (99% +/- 13%, 90% +/- 10%, 63% +/- 6%, 51% +/- 10%, and 27% +/- 4%), endothelium-independent vasodilation (93% +/- 3%, 86% +/- 2%, 78% +/- 5%, 61% +/- 5%, and 38% +/- 9%), and endothelium-dependent vasodilation (93% +/- 3%, 96% +/- 2%, 94% +/- 2%, 87% +/- 7%, and 62% +/- 11%). There were similar time-dependent deteriorations in mesenteries subjected to ischemia coupled with cardioplegic solution that were not significantly different from any of the ischemia-alone groups when matched for ischemic times. Thus, for example, after 180 minutes of ischemia alone, the vasoconstrictor response was 18% +/- 3%, endothelium-independent vasodilation was 44% +/- 7%, and endothelium-dependent vasodilation was 40% +/- 9%. The results demonstrate that under the conditions of this experiment, the St. Thomas' Hospital cardioplegic solution neither protects nor injures the vasculature during an episode of ischemia and reperfusion. However, in studies with 150 minutes of normothermic ischemia, multiple infusions of cardioplegic solution (given every 30 minutes during ischemia) resulted in protection of smooth muscle and endothelial function. Thus, after multiple infusions, vasoconstriction to phenylephrine was 74% +/- 4%, vasodilation to nitroprusside was 81% +/- 6%, and vasodilation to adenosine triphosphate was 89% +/- 5%. In conclusion, when the St. Thomas' Hospital cardioplegic solution is used as a single infusion and coupled with ischemia, the solution fails to protect smooth muscle and endothelial function against ischemic injury, but some protection is obtained when the solution is infused intermittently throughout the ischemic period.

Animals↗

University of Wisconsin solution versus Stanford cardioplegic solution and the development of cardiac allograft vasculopathy.

BACKGROUND: University of Wisconsin (intracellular) solution has been shown to offer some distinct benefits of myocardial preservation over Stanford (extracellular) solution, including a more rapid functional recovery, improved adenosine triphosphate preservation, and a tendency for less postoperative inotropic agents. However intracellular solutions with high potassium content have been reported to cause a functional if not structural endothelial injury in laboratory experiments. METHODS: Because of this information we retrospectively viewed our follow-up angiographic data for the development of the cardiac allograft vasculopathy in a consecutive series of 195 heart transplant recipients. These patients were treated in identical fashion, with the same immunosuppression regimen, except for the type of cardioplegia used--Stanford solution (group I n = 95) and University of Wisconsin solution (group II n = 100). RESULTS: With a mean follow-up of 24 months after transplantation, a significant difference was seen in the development of cardiac allograft vasculopathy in group II (22%) versus group I (14%, p < 0.03). Although significant differences were observed with univariate analysis with respect to donor age and ischemic time favoring group I and with multivariate statistical analysis with respect to overall rejections favoring group II, the only significant variable for the difference in the development of allograft vasculopathy was University of Wisconsin cardioplegic solution (p < 0.003). A subgroup of 30 patients previously randomized for a functional study comparing the two cardioplegic agents showed a tendency for statistical significance with a freedom from allograft vasculopathy of 93% in group I, as compared with 83% in group II, after 13 months follow-up (p = 0.09). The overall probability of being free of vasculopathy at 24 months was 86% for group I and 70% for group II. CONCLUSIONS: The data support the conclusion that University of Wisconsin intracellular solution is associated with an increased incidence of vasculopathy versus Stanford solution and warrants investigation for modification of this preservation agent in heart transplantation.

Adenosine↗

[Ionic bases of cardioplegic solutions. II. Influence of the ionic composition of a cardioplegic solution on the metabolic and functional preservation of ischemic myocardium. Experimental evaluation with phosphorus 31 nuclear magnetic resonance and applications to cardiac surgery].

The object of this study was to establish whether the protective effects of a cardioplegic solution could be improved by ionic or pharmacological intervention aimed at reducing cellular Ca++ overload resulting from myocardial ischaemia. The experimental model was the isolated perfused working heart of the rat submitted to 60 or 120 minutes of hypothermic ischaemia (15 degrees C) followed by 30 minutes of reperfusion at 37 degrees C. The high energy phosphates were measured every 2,5 or 5 minutes by Phosphorus 31 (P31) nuclear magnetic resonance and correlated with haemodynamic data. Our results showed that the best metabolic (75,5 +/- 9,7 p. 100 preservation of ATP after 60 minutes ischaemia) and functional protection (91,8 +/- 4,7 p. 100 recovery of aortic output after 30 minutes reperfusion) was obtained with a solution with the following ionic properties: 1) high Mg++ concentration (13 mM); 2) low Ca++ concentration (0,25 mM); 3) high Na+ concentration (100 mM). The protective effects of this solution were further improved by the addition of a calcium blocking agent (nifedipine 0,2 micrograms/ml). This preserved 85,5 +/- 3,2 p. 100 of basal ATP values after 120 minutes of ischaemia and was associated with a 92,9 +/- 2,8 p. 100 recovery of aortic output at the end of reperfusion. We conclude that: 1) limitation of cellular Ca++ overload is one of the major objectives to be considered when making up cardioplegic solutions; 2) the use of P 31 nuclear magnetic resonance on the isolated working heart is the technique of choice for comparing methods of myocardial protection because it provides a non-invasive, sequential and simultaneous assessment of the parameters of metabolic and haemodynamic function.

Adenosine Triphosphate↗

Comparison of clinical outcome between histidine-triptophan-ketoglutalate solution and cold blood cardioplegic solution in mitral valve replacement.

BACKGROUND: This study was conducted to compare the effect of histidine-triptophan-ketoglutalate solution (HTK) with that of cold blood cardioplegic solution (CBC) in mitral valve surgery. METHOD: Forty-six patients who underwent mitral valve replacement between January 1994 and December 1996 were enrolled in this study. Twenty patients received HTK (HTK group), while 27 patients had CBC (CBC group) as myocardial protection. HTK was given as a single high dose, whereas CBC was used in the usual multidose format. RESULT: The doses of inotropic agent at the end of extracorporeal circulation did not differ between the HTK group and the CBC group. Creatine kinase values (units) on day 1 and day 2 were 1140+/-412, 921+/-436 for the HTK group and 904+/-335, 816+/-420 for the CBC group, respectively (p = NS). Spontaneous defibrillation occurred in 26% of the CBC group and 90% of the HTK group (p < 0.05). Pacing was temporarily used in 20% of the HTK group and 44% of the CBC group after extracorporeal circulation (p < 0.05). CONCLUSIONS: These results suggest that HTK provided more adequate myocardial protection in mitral valve surgery.

Blood↗

Hypothermic preservation of isolated rat lungs in modified bicarbonate buffer, EuroCollins solution or St Thomas' Hospital cardioplegic solution.

OBJECTIVES: Inadequate preservation solutions limit lung storage times and, consequently, transplant programs. To address this problem we established an isolated, ventilated and perfused rat lung preparation. Here we report the effects of hypothermic storage in EuroCollins solution, St Thomas' Hospital cardioplegic solution and a modified bicarbonate buffer solution. METHODS: Lungs from male Wistar rats (230-330 g) were perfused via the pulmonary artery with modified bicarbonate buffer (37 degrees C, 15 ml/min, constant flow) and ventilated by positive pressure (tidal volume:1.6-1.8 ml, 80 breaths/min). Vascular resistance (pulmonary artery pressure:perfusate flow ratio) and airways compliance (tidal volume:tracheal pressure ratio) were measured. After a control perfusion period (20 min), lungs were flushed with, then immersed in, bicarbonate buffer (4 degrees C) for varying periods (0-24 h). After storage, lung function was assessed during 20 min reperfusion. Having established a suitable period for study, storage in EuroCollins, St Thomas' Hospital cardioplegic solution or bicarbonate buffer were compared. RESULTS: Pulmonary compliance (ml/cmH2O) was significantly (P < 0.05) reduced in lungs stored for 6 h in modified bicarbonate buffer (0.026 +/- 0.008), EuroCollins solution (0.013 +/- 0.002) or St Thomas' Hospital solution (0.025 +/- 0.005) compared to unstored lungs (0.068 +/- 0.007). Vascular resistance, (1.32 +/- 0.13 cmH2O/ml per min) in unstored lungs, was similar in lungs stored in St Thomas' Hospital solution but increased significantly in lungs stored in modified bicarbonate buffer (3.22 +/- 0.78 cmH2O/ml per min) or EuroCollins solution (4.66 +/- 0.57 cmH2O/ml per min). CONCLUSIONS: Hypothermic storage of rat lungs for 6 h in modified bicarbonate buffer or St Thomas' Hospital solution causes less increase in vascular resistance on reperfusion than EuroCollins solution.

Animals↗

Extended cardiopulmonary preservation: University of Wisconsin solution versus Bretschneider's cardioplegic solution.

Application of the University of Wisconsin cold storage solution has rapidly expanded to include medium-term to long-term preservation of virtually all intraabdominal organs. Its use in intrathoracic organ transplantation has also been suggested. We therefore examined the efficacy of the University of Wisconsin solution in a primate allotransplantation model for preservation of hearts, and as a simple single-solution system for static preservation of heart-lung blocks, for periods of ischemia ranging from 6 to 24 hours. For comparison, we employed the histidine-tryptophane-ketoglutarate cardioplegic solution of Bretschneider. University of Wisconsin solution provided superior results with regard to clinical outcome and hemodynamic recovery of hearts after ischemic periods of up to 16 hours. This was in contrast to Bretschneider's solution, which allowed storage of hearts for periods of only up to 10 hours. Heart-lung blocks were equally well preserved with either University of Wisconsin or Bretschneider's solution after 6 to 12 hours, although the University of Wisconsin solution group exhibited a more notable increase in pulmonary water content. This was in accordance with histological data, which suggested that, although hemodynamic recovery of hearts stored for periods longer than 10 hours was poor, preservation of pulmonary ultrastructure was far superior using Bretschneider's solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours.

Adenosine↗

Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations.

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.

Cardioplegic Solutions↗

Effects of oxygenated cardioplegic solutions on myocardial aerobic metabolism.

Oxygenated cardioplegic solutions can deliver sufficient oxygen to support aerobic metabolism of heart tissue during cardiac arrest, but little is known about oxygen use after cardioplegic solution infusion. Exhaustion of myocardial oxygen stores after infusion of oxygenated crystalloid cardioplegic solution or Krebs-Henseleit buffer was measured in rat hearts. Since nicotinamide adenine dinucleotide accumulates when mitochondria become anaerobic, the epicardium was monitored during perfusion and ischemia. As ischemia progressed, nicotinamide adenine dinucleotide fluorescence increased, indicating exhaustion of oxygen. After buffer perfusion, at 37 degrees C, 50% of peak fluorescence was seen at 13 +/- 1 seconds and 90% at 37 +/- 3 seconds. Oxygenated cardioplegic solution increased these intervals to 57 +/- 6 and 114 +/- 9 seconds, respectively. Oxygenated cardioplegic solution at 10 degrees C increased the time to 50% fluorescence to 238 +/- 12 seconds and to 90% to 320 +/- 14 seconds. Differences between buffer and cardioplegic solution were less at 10 degrees C. Aerobic metabolism was completely abolished 6 minutes after infusion of 10 degrees C oxygenated cardioplegic solution. Maintenance of continuous aerobic metabolism during surgical cardiac arrest would require frequent administration of oxygenated crystalloid cardioplegic solution.

Aerobiosis↗

University of Wisconsin solution provides superior myocardial preservation compared with Stanford cardioplegic solution.

The efficacy of the University of Wisconsin solution to safely prolong preservation times for kidney, pancreas, and liver transplantation is established, but its efficacy in enhancing myocardial preservation is not yet clear. We studied the effects of Stanford cardioplegic solution and the University of Wisconsin solution both in preserving the myocardium and in protecting it from the effects of reperfusion injury after 6 hours of preservation. In 28 rat hearts we measured changes in high-energy phosphate content (with magnetic resonance spectroscopy) and histologic changes (edema, endothelial changes, myocyte architecture) during preservation and changes in high-energy phosphate content, histologic status, and performance (aortic systolic and diastolic pressure, heart rate, rhythm) in Langendorff and working hearts during reperfusion. No significant differences in the kinetics of high-energy phosphate changes were noted between the two cardioplegic solutions during preservation. However, at the end of 6 hours of preservation, hearts in the Stanford cardioplegic solution group were more edematous (p < 0.01) than those in the University of Wisconsin group. During reperfusion, no significant differences in the kinetics of high-energy phosphates were noted between the two cardioplegic solutions. None of the hearts in the University of Wisconsin solution group developed ventricular fibrillation at the start of reperfusion, but all hearts in the Stanford group did so. Once sinus rhythm was established no significant differences in developed pressure or heart rate were found between the two solutions. After 2.5 hours of reperfusion, hearts in the Stanford group were more edematous (p < 0.002) and had a greater disruption of myocyte architecture (p < 0.002) and greater arteriolar endothelial injury (p < 0.004). In conclusion, the University of Wisconsin solution better protects the myocardium in this rat model than does Stanford solution. The mechanism for this beneficial effect of the University of Wisconsin solution appears to be due to its better preservation of the microvasculature rather than differences in preservation of high-energy phosphates.

Adenosine↗

Myocardial "equilibration processes" and myocardial energy turnover during initiation of artificial cardiac arrest with cardioplegic solution - reasons for a sufficiently long cardioplegic perfusion.

In canine hearts the myocardial equilibration processes (temperature, pO2, pCO2, Na+, K+) and the myocardial energy turnover were analyzed at the beginning of a cardioplegically induced cardiac arrest during a coronary perfusion of 10 minutes. The investigated hearts (n = 10) were perfused with the Bretschneider histidine-buffered cardioplegic solution according to the recommendations worked out for clinical use. The results show that during the cardioplegic coronary perfusion of 10 minutes the cooling and temperature equilibration of the myocardium occur considerably faster than the establishment of a new energy steady-state at a very low level. The minimalization of the coronary resistance and of the myocardial O2 consumption are only reached after an extended perfusion period of 7 to 9 minutes. In consequence of the results, the following recommendations can be given for the clinical use of the Bretschneider cardioplegic solution: a) the solution should be used at a temperature of between 5 degrees and 10 degrees C, b) the cardioplegic coronary flow should be between 60 and 80 ml/min . 100 gww, c) the human heart should be perfused for 8 to 10 minutes and, d) the perfusion pressure should be maintained at 40 to 50 mmHg after cardiac arrest has set in. So far the action of equilibration procedures when using the Bretschneider cardioplegic method has not been compared with that of other cardioplegic methods.

Animals↗

Nifedipine stability in cardioplegic solution.

The stability of nifedipine in cardioplegic solution was studied. Cardioplegic solutions containing nifedipine at 275 and 500 micrograms/liter were stored in plastic bags covered in brown plastic wrappers (1) under normal room light at 25 degrees C and (2) in a dark refrigerator at 4 degrees C. Samples were removed periodically for 48 hours. Infusions of cardioplegic solution containing 275 micrograms/liter were simulated using tubing and flow rates of 100, 200, and 300 ml/min; bags were covered with aluminum foil, while tubing was exposed to normal room lighting or yellow lighting, which does not degrade nifedipine. Gas chromatography was used for nifedipine assays. Nifedipine degraded more rapidly at 25 degrees C than at 4 degrees C. However, even when protected from light and refrigerated, nifedipine concentrations declined to less than 90% of original potency by approximately six hours after preparation. There was no significant degradation during the simulated infusion regardless of light exposure or flow rate. Cardioplegic solutions containing nifedipine should be prepared immediately before the surgical procedure, refrigerated until use, and protected from light until administration.

Cardiovascular Agents↗

Collins' solution for cold storage of the heart for transplantation must be reversed with cardioplegic solution before reperfusion. A functional and metabolic study in the rat heart.

The following hypotheses were tested using an isolated perfused working rat heart model: (1) Collins' solution for cold storage of the heart is harmful for the heart during reperfusion; (2) a "reverse" of the intracellular-type Collins' solution with an extracellular-type cardioplegic solution before reperfusion is able to prevent this disadvantage of Collins' solution. The following two major groups (I and II) and five subgroups (-a to -e) in each group were prepared. In group I (reversed group); the hearts were initially stored in Collins' solution but were reversed by a 1-minute flush with cardioplegic solution followed by storage in cardioplegic solution for the last 1 to 180 minutes of the total 3-hour storage, that is, groups I-a (reversed for 1 minute), I-b (10 minutes), I-c (30 minutes), I-d (90 minutes), and I-e (180 minutes). In group II (nonreversed control group); the hearts were stored in Collins' solution throughout 3 hours and were also divided into five subgroups of groups II-a, II-b, II-c, II-d, and II-e in which only a 1-minute flush with Collins' solution was performed at the point corresponding to group I. The coronary flow in any of group II showed a marked decrease during the early reperfusion period. In group I, however, the coronary flow increased significantly in proportion to the duration of the reversing phase. The recovery of the aortic flow and the cardiac output in group I showed a bell-shaped pattern in relation to the duration of the reversing phase, reaching their peak values when reversed for 30 minutes (group I-c). The prolonged reverse (180 minutes) resulted in a deterioration of functional recovery associated with a poorer preservation of high-energy phosphates and a larger enzyme leakage. These results suggest that the beneficial effects of intracellular-type Collins' solution for cold storage of the heart were further improved by reversing Collins' solution with the extracellular-type cardioplegic solution for the last 30 minutes of the 3-hour cold storage because the disadvantageous vasoconstriction due to Collins' solution during reperfusion was successfully prevented by the replacement of intravascular and extravascular Collins' solution with cardioplegic solution before the reperfusion.

Animals↗