Myocardial energy metabolism in asphyxiated canine hearts preserved for 24 hours.

Myocardial energy metabolism in asphyxiated cadaver hearts preserved in UW solution (UWS; group 1, n = 6) or modified Collins' solution (MCS; group 2, n = 6) was compared with that in cardioplegic arrested hearts immersed in ice-cold MCS with (group 3, n = 6) or without myoprotective drugs (group 4, n = 5). All hearts were stored for 24 hr. The hearts in groups 1 and 2 were pretreated with prostacyclin, verapamil, and propranolol; asphyxiated for 10 min, reversed by coronary perfusion with warm blood cardioplegia (WBCP); perfused with ice-cold crystalloid cardioplegia for 2 hr; excised and immersed in cold storage solution for 22 hr; and perfused again with WBCP before reperfusion. ATP contents were measured in biopsy specimens by HPLC. Myocardial ATP level decreased significantly from 23.7 +/- 1.7 to 15.9 +/- 2.5 mumol/g dry wt. (P less than 0.0001) by asphyxia, but recovered to within normal limits by WBCP in group 1. The ATP level again decreased to 15.8 +/- 2.4 mumol/g dry wt. during 24-hr storage, but finally rose to 22.4 +/- 3.5 mumol/g dry wt. by terminal WBCP. The ATP metabolism in group 2 was similar to that in group 1. The ATP content in group 4 was significantly lower than that in other groups (P less than 0.01) after 24-hr preservation. The study shows that damage to cadaver hearts can be reversed and the hearts maintained satisfactorily viable for 24 hr.     

Prolonged preservation of cadaver heart with Belzer UW solution: 24-hour storage system for asphyxiated canine hearts

The efficacy of Belzer UW solution was compared to Collins' solution in the preservation of asphyxiated cadaver hearts in a canine model. Donor hearts were stored for 24 h: 2 h of in situ hypothermic (15 degrees C) coronary perfusion plus 22 h of simple immersion in ice-cold solution. Verapamil, propranolol and prostacyclin were used for myocytoprotection in both groups. After orthotopic transplantation, all animals were weaned off bypass without inotropic support. After 1 h, however, the cardiac output was significantly higher in the Belzer UW solution group (128 +/- 28 vs. 67 +/- 13 ml/kg/min, p less than 0.01).     

Morphology of canine hearts after 24 hours' preservation and orthotopic transplantation.

Ten dogs underwent orthotopic cardiac transplantation after preservation of the donor heart for 24 hours in an oxygenated hypothermic, hypertonic, intracellular solution, either with (five dogs) or without (five dogs) continuous, oxygenated, low-pressure perfusion. Eight dogs survived for 24 hours after transplantation, at which time they were put to death. The two nonsurvivors were among the five with nonperfused hearts. Examination of all 10 donor hearts showed differences between the two groups: Four of five nonperfused hearts showed severe transmural myocardial coagulation necrosis but only small foci of contraction band necrosis (myofibrillar degeneration). The perfused hearts, however, showed more extensive subendocardial areas of contraction-band necrosis, but only minimal and focal coagulation necrosis, indicating less severe hypoxic damage. These results indicate that oxygenated perfusion with a hypothermic, hypertonic, intracellular solution may permit improved transplant survival after extended cardiac preservation.     

Direct effects of propofol on myocardial contractility in in situ canine hearts.

The pronounced decrease in arterial blood pressure evident during anesthetic induction with propofol has raised the possibility that propofol has a direct negative inotropic effect. Previous attempts to evaluate this mechanism in vivo have been inconclusive because of confounding variables associated with intravenous administration of propofol. Accordingly, in the current study, steady-state changes in myocardial contractility and related hemodynamic parameters were assessed during intracoronary infusions of propofol in seven open-chest dogs anesthetized with fentanyl and midazolam. The left anterior descending coronary artery (LAD) was cannulated and perfused at controlled pressure (100 mmHg) with normal arterial blood. In LAD-perfused myocardium, contractility was evaluated from measurements of percent segmental shortening (%SS) obtained with ultrasonic crystals. Coronary blood flow in LAD was measured electromagnetically and used to calculate myocardial oxygen consumption (MVO2; Fick principle) and coronary propofol concentration. Propofol was infused into the LAD at 150, 300, 600, and 1,200 micrograms/min (P-150, P-300, P-600, P-1,200). These infusion rates yielded calculated blood concentrations of 7 +/- 1, 15 +/- 1, 26 +/- 2, and 50 +/- 5 micrograms.ml-1, respectively. The calculated blood concentrations at P-150 were in the clinical range, whereas those at P-300, P-600, and P-1,200 were supratherapeutic. P-150 had no effect on %SS, whereas higher infusion rates caused decreases in %SS. Changes in MVO2 by propofol generally paralleled changes in %SS. At P-150 and P-300, coronary blood flow was proportional to MVO2, whereas at P-600 and P-1,200, coronary blood flow was in excess of the prevailing MVO2, resulting in increased coronary venous oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resuscitation and evaluation of non-beating hearts obtained from asphyxiated dogs via autoperfusing heart-lung circuit.

BACKGROUND: The shortage of donor hearts has made use of non-beating hearts as cardiac grafts an attractive possibility for heart transplant candidates. The purpose of this study was to evaluate the utility of leukocyte-depleted hot shot cardioplegia for resuscitation of non-beating hearts obtained from asphyxiated dogs via an autoperfusing heart-lung circuit. METHODS: Mongrel dogs were divided into 3 groups according to the warm ischemia time and the method of reperfusion before starting the autoperfusing heart-lung circuit. Group A (n=4) had 60 minutes of warm ischemia and reperfusion without leukocyte-depleted hot shot, Group B (n=5) had 30 minutes of warm ischemia and reperfusion with leukocyte-depleted hot shot, and Group C (n=7) had 60 minutes of warm ischemia and reperfusion with leukocyte-depleted hot shot. We calculated stroke work via the heart-lung circuit to evaluate cardiac function of the resuscitated hearts. The criteria for "recovery" has been reported elsewhere. Myocardial water content of the resuscitated hearts was also measured and analyzed. No inotropic agents were used. RESULTS: The recovery rates in groups A, B and C were 0%, 80% and 57%, respectively, and the group B rate was significantly higher than the group A rate (p=0.04). Although myocardial water content did not differ between groups B and C, it was significantly lower in recovered hearts than in non-recovered hearts (p=0.04). Significant negative correlation was observed between the maximum stroke work value and myocardial water content in the resuscitated hearts (r=0.668, p=0.03). CONCLUSIONS: The autoperfusing heart-lung circuit is useful for evaluation and maintenance of cardiac function. Our experimental data shows that leukocyte-depleted hot shot plays a great role for resuscitation and recovery of non-beating hearts.     

Regression and recovery of well-developed coronary collateral function in canine hearts after aorta-coronary bypass

After restoration of antegrade blood flow by coronary artery bypass grafting to a region of myocardium supplied by well-developed collateral vessels, there is regression of collateral supply to that region. There is controversy as to how rapidly this regression occurs, how soon collateral flow might return after an acute occlusion of the bypass graft, and how effective pharmacologic agents such as nitroglycerin might be in accelerating this return. To investigate this problem, 14 canine hearts were collateralized by Ameroid occlusion of the left anterior descending coronary artery. Regression and recovery of well-developed collateral function were studied after opening and closing an aorta-coronary bypass. Before bypass, peripheral coronary pressure was 82 +/- 2 mm Hg, retrograde flow 63 +/- 7 ml/min, collateral flow 21 +/- 2 ml/min, and collateral resistance 0.96 +/- 0.13 mm Hg/ml/min. One hundred minutes of bypass perfusion significantly decreased peripheral coronary pressure by 27%, retrograde flow by 52%, and collateral flow by 42%, and significantly increased collateral resistance by 319%. When the bypass was acutely occluded for 30 minutes, collateral resistance decreased spontaneously by 37%. When intracoronary nitroglycerin was administered for 5 minutes immediately after bypass occlusion, collateral resistance rapidly decreased by 72%, but subsequent collateral regression was not alleviated. Increased flow through regressed collateral vessels during retrograde flow diversion was associated with a decrease in collateral resistance. Results demonstrate rapid but not instantaneous regression and recovery of mature collateral function in response to requirements of collateral-dependent myocardium. Regressed collateral vessels can be dilated by nitroglycerin. Flow-dependent changes in collateral vascular tone appear to be responsible for early regression and recovery of collateral function.     

Cardiac function of transplanted rat hearts using a working heart model assessed by magnetic resonance imaging.

BACKGROUND: A direct correlation between graft rejection and cardiac contractile function in small-animal models has been difficult to establish because (i) the conventional non-working heart model is greatly different from the orthotopic heart in terms of left ventricular work and (ii) it is difficult to obtain hemodynamic data in situ. We have used magnetic resonance imaging (MRI) techniques to obtain noninvasive, in-situ quantitation of ventricular volume after heterotopic cardiac transplantation. METHODS: Infra-renal heterotopic cardiac transplantation was performed on rats using syngeneic and allogeneic untreated donors in both working and non-working left heart models. An occluding balloon catheter in the inferior vena cava was used to vary the pre-load to the graft. An arteriovenous fistula was created to raise inferior caval oxygen saturation. Magnetic resonance imaging measurements were carried out at day 3, 4, and 5 post-transplantation. Left ventricle end-diastolic and end-systolic volumes were calculated using a biplanar ellipsoid model. RESULTS: Stroke volume was significantly increased in the working heart model as compared to the non-working model. At day 4 post-transplant, the diastolic pressure-volume relationship in the allograft group was significantly shifted, indicative of decreased myocardial distensibility, whereas the indices of systolic function were preserved. CONCLUSIONS: We have developed a heterotopic transplant working rat heart model and have used it to assess in-situ cardiac function by MRI. Sensitive indices of diastolic contractile function can be obtained in this rodent transplant model that correlate well with histologic evidence of early rejection.     

Acid-base determinations in normal and asphyxiated term infants during the first 24 hours of life.

Vigorous term infants who are born normally initially have a moderate metabolic and respiratory acidosis which is corrected by the time the infant is 6 hours old. Asphyxiated infants consistently show a greater degree of acidosis, both metabolic and respiratory. Caesarean section results in higher pCO2 values, especially when 'diffusion apnoea' occurs. Indications for the correction of acidosis in asphyxia are proposed.     

Nicardipine: myocardial protection in isolated working hearts.

The effectiveness of the calcium antagonist nicardipine in protecting the ischemic myocardium was evaluated using the hemodynamic recovery of isolated working rat hearts subjected to hyperkalemic cardiac arrest followed by ischemia at 37.5 degrees C and 10 degrees C. Rat hearts (n = 51) received 20 mL of cardioplegia and were subjected to 27 minutes of ischemia at 37.5 degrees C. Group A (control) did not receive nicardipine. Groups B through F received nicardipine in the cardioplegia with total doses ranging from 2 micrograms to 6 micrograms. Group A had 46% survival of ischemia, whereas groups C (3 micrograms) and D (4 micrograms) had survival rates of 88% and 100%, respectively (p less than 0.05). The recovery of aortic flow after ischemia was 35% in group A, compared with 76% in group B (2 micrograms) and 81% in group D (p less than 0.05). Group A had 49% postischemic recovery of cardiac output, whereas groups B and D had 82% and 85% recovery (p less than 0.05). The postischemic recovery of stroke volume was 48% in group A compared with 84% in group B, 87% in group D, and 73% in group E (5 micrograms) (p less than 0.05). Additional rats were exposed to 210 minutes of ischemia (n = 41) or 240 minutes of ischemia (n = 56) at 10 degrees C. Control groups did not receive nicardipine, whereas treatment groups received nicardipine in the cardioplegia with total doses ranging from 1.4 micrograms to 6.4 micrograms. There were no significant differences in the survival of ischemia or the recovery of function after ischemia at 10 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrionatriuretic peptide improves left ventricular function after myocardial global ischemia-reperfusion in hypoxic hearts

Atrionatriuretic peptide (ANP) is reported to be useful for attenuating myocardial ischemia–reperfusion injury and improving left ventricular function after reperfusion. However, ANP may be either ineffectual or harmful in cases where the myocardium has been chronically hypoxic since birth. This can be a result of the concomitant high levels of cyclic guanosine monophosphate (cGMP) produced within the myocardium. This study aimed to verify the validity of using ANP to improve left ventricular function after myocardial ischemia–reperfusion injury. For this purpose, a cyanotic congenital disease model that was developed using isolated rat hearts was used. Hearts were obtained from Sprague‐Dawley rats that were housed from birth until 6 weeks of age either in a hypoxic environment with 13–14% FiO₂ (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1 µM) into the reperfusion solution was compared with those hearts that were not administered ANP in both hypoxic (without ANP: n = 6, with ANP: n = 6, with ANP and HS‐142‐1[an antagonist of ANP]: n = 6) and normoxic hearts (without ANP: n = 6, with ANP: n = 6). In the hypoxic hearts, ANP administration improved the percent recovery of the left ventricular developed pressure (76.3 ± 9.2% without ANP vs. 86.9 ± 6.7% with ANP), maximum first derivative of the left ventricular pressure (82.4 ± 1.1% without ANP vs. 95.8 ± 6.5% with ANP), and heart rate (85.6 ± 4.7% without ANP vs. 96.1 ± 5.2% with ANP) after reperfusion. The improvement and recovery of these cardiac functions were closely related to significantly increased levels of postischemic cGMP release after ANP administration. The effect of ANP was blocked by HS‐142‐1. The improvements observed in the hypoxic group were similar to those found in the normoxic group. ANP administration during reperfusion improved left ventricular function after myocardial acute global ischemia–reperfusion equally in both the chronically hypoxic and age‐matched normoxic groups.     

Halothane, enflurane and isoflurane on abnormal automaticity and triggered rhythmic activity of Purkinje fibers from 24-hour-old infarcted canine hearts

The effects of inhalation anesthetics halothane, enflurane, and isoflurane on spontaneous impulse initiation (automaticity) and triggered sustained rhythmic activity were examined in Purkinje fibers derived from normal (n = 38) and 24-h-old infarcted canine hearts (n = 27) to further understanding of their influence on the cellular mechanisms underlying generation of cardiac arrhythmias. Purkinje fibers from normal or infarcted hearts were superfused with modified Krebs' solution (37 degrees C) with or without epinephrine (2 or 15 microM) and equilibrated with a 97% O2-3% CO2 gas mixture (control). Transmembrane action potentials were recorded using conventional microelectrode techniques, and Purkinje fibers were exposed to anesthetic concentrations equivalent to 2.0 MAC. Normal Purkinje fibers were not spontaneously active unless exposed to epinephrine. All anesthetics (enflurane greater than halothane, isoflurane; P less than 0.05) increased automaticity of normal Purkinje fibers exposed to either epinephrine concentration. Partially depolarized Purkinje fibers from infarcted hearts were either spontaneously active or were quiescent. For ischemic fibers that beat spontaneously, abnormal automaticity was sustained (duration greater than 300 s) or periodic (duration less than 300 s). Sustained abnormal automaticity was elicited by epinephrine (15 microM) in some quiescent partially depolarized fibers. None of the anesthetics affected the rate of sustained abnormal automaticity, regardless of whether the induction of such automaticity required epinephrine, nor did anesthetics significantly affect the duration of trains of periodic abnormal automaticity. Finally, quiescent, partially depolarized Purkinje fibers were tested for triggered rhythmic activity during pacing at a cycle length of 800 ms.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new model for assessment of myocardial function: I. Description and performance norms.

Use of a new isometric rabbit-heart model, a modification of Langer's original preparation, has permitted independent assessment of myocardial perfusability in addition to contractility and relaxation. In this model an isolated, paced, interventricular septum contracts against a tension transducer and is perfused from another awake rabbit. Heparinized, diluted arterial blood is warmed and pumped at 1 ml/g-min. Perfusion pressure is measured by transducer. Each preparation serves as its own control. This model was used in determining performance norms for 68 preparations. Contractility was measured by maximum active tension, maximum rate of increase of tension and time to peak tension; relaxation by resting tension, maximum rate of relaxation and relaxation time; and perfusability by mean perfusion pressure and mean conductance. The status of the parabiotic rabbit was closely monitored. These studies have shown that the model is relatively simple, clearly defined and adaptable to a variety of experimental protocols.