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The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia. 139 43

Successful long-term myocardial preservation is dependent on optimizing conditions during arrest, storage, and reperfusion. Neonatal piglet hearts were arrested and stored in University of Wisconsin solution (UW) at 4 degrees C for 24 hours and reperfused on a blood-perfused, adult animal-supported isolated circuit. Results were compared with nonischemic continuously perfused control hearts (group 1, n = 5). The initial 10 minutes of reperfusion in groups 2-4 was modified by aspartate/glutamate-enriched leukocyte-depleted blood cardioplegia (group 2, n = 7), leukocyte depletion alone (group 3, n = 9), and aspartate/glutamate-enriched blood cardioplegia alone (group 4, n = 6). After 10 minutes, perfusion was continued with unmodified whole blood. In group 5 (n = 9), unmodified whole blood was used for initial reperfusion as well as subsequent perfusion. The stroke work index was determined 60 minutes after reperfusion. Biopsies for high-energy phosphates, myocardial water content, and electron microscopy were obtained after functional assessment. The stroke work index at left ventricular end-diastolic pressure of 9 mm Hg did not differ between groups 1 and 2 (19.0 +/- 1.4 x 10(3) and 19.0 +/- 1.5 x 10(3) [mean +/- SEM] erg/g, respectively). These were both different from group 5 (13.3 +/- 0.8 x 10(3) erg/g, p less than 0.05). Group 3 showed improved function (15.7 +/- 0.7 x 10(3) erg/g), but this did not reach statistical significance when compared with group 5. No difference was found between groups 4 and 5. Myocardial water content, high-energy phosphate levels, and ultrastructure were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complete functional recovery after 24-hour heart preservation with University of Wisconsin solution and modified reperfusion. 168 70

Open-chest sheep underwent 90 minutes' occlusion of the diagonal branch of the left anterior descending coronary artery, followed by vented cardiopulmonary bypass. After 30 minutes of cardioplegic arrest, simulating distal anastomoses, the occlusion on the coronary artery branch was released. Controlled reperfusion (40 to 50 mm Hg, 135 to 150 ml/min) for the first 20 minutes was delivered at the aortic root with either unmodified whole blood (control, n = 7) or blood passed through leukocyte filters (filters, n = 7). Serial measurements were made during 3 additional hours reperfusion off cardiopulmonary bypass. During ischemia, the major determinants of infarct size, which include area at risk, collateral myocardial blood flow, and rate-pressure product were not significantly different between groups. Overall, during reperfusion, mean left ventricular stroke work index in the filter group was greater than in the control group (28.7 +/- 5.8 versus 12.6 +/- 6.4 x 10(3) erg/gm, p less than 0.05), as was mean rate of rise of left ventricular pressure (1900 +/- 260 versus 1348 +/- 279 mm Hg/sec, p less than 0.05). Myocardial blood flow to the area at risk at 3 1/2 hours of reperfusion in the filter group was also significantly better than in the control group (0.57 +/- 0.15 versus 0.27 +/- 0.05 ml/min/gm, p less than 0.05), as was necrotic area as a percentage of area at risk (40% +/- 6% versus 70% +/- 5%, p less than 0.05). These results demonstrate amelioration of myocardial stunning and the no-reflow phenomenon, as well as decreased infarct size. We conclude that controlled reperfusion with leukocyte-depleted blood is superior to whole-blood reperfusion for the surgical treatment of acute regional ischemia.
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PMID:Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size. 172 16

Canine left latissimus dorsi (LD) muscles were used to construct two kinds of skeletal muscle powered ventricles (SMPV): a double layered small size (10-17 mL) SMPV (A), and a single-layered large size (40-70 mL) SMPV (B). The same muscle was used sequentially for the construction of both SMPV. A mock circulation system was used for testing. This allowed for change of the preload (10-60 mmHg) and afterload (40-160 mmHg) independently. The peak developed pressure (PDP) and stroke volume (SV) were measured, and the stroke work (SW) was analyzed on line by a computer. The isovolumic PDP was 93.3 +/- 11.8 mmHg at 10 mmHg preload, and 157.7 +/- 20.2 mmHg at 60 mmHg for A, and 37.8 +/- 5.5 mHg and 107.8 +/- 8.5 mmHg for B. The SV and SW at 50 mmHg preload and 80 mmHg afterload were 18.30 +/- 1.25 mL and 1.06 +/- 0.10 x 10(6) erg for A, and 34.18 +/- 2.36 mL and 2.51 +/- 0.28 x 10(6) erg for B. The SV and SW at 20 mmHg preload and 160 mmHg afterload were 2.65 +/- 0.31 mL and 0.27 +/- 0.05 x 10(6) erg for A, and 1.03 +/- 0.23 mL and 0.04 +/- 0.01 x 10(6) erg for (B). The SW generated by the large single-layered SMPV is similar to that reported for the canine left ventricle but requires a high preload. The large single-layered SMPV showed a higher dependence on pre- and afterload changes than the double layered small SMPV, which generates a higher pressure even at low preloads.
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PMID:Skeletal muscle powered ventricle: comparison of double-layered small ventricle and single-layered large ventricle. 180 98

The present study addressed the filling sensitivity and power output of the TOYOBO VAD (TVAD) and Utah soft artificial ventricle (USAV) to evaluate these pumps as a muscle powered cardiac assist device (MCAD). Two pumps were assembled with three different types of driving chambers placed underneath the latissimus dorsi (LD) muscle: the soft spindle (SS) type, elastic spindle (ES) type and bellows (B) type. The USAV required a filling time of greater than 1000 msec at any preload with any driving chamber, although the TVAD allowed this only with the ES-type chamber assembly. In an ex vivo mock study, the ES- and SS-type chamber assembly demonstrated a maximum stroke volume (SV) of 7.7 mL (39% stroke) by the USAV and 12 mL (17% stroke) by the TVAD at an afterload below 20 mmHg. On the other hand, the B-type chamber increased SV according to afterload in both pumps, resulting in a maximum SV of 25 mL (36% stroke) by the TVAD and 7.6 mL (38% stroke) by the USAV at a 30 mmHg afterload. The maximum stroke work (SW) achieved was 1.3 x 10(6) erg by the TVAD and 0.5 x 10(6) erg by the USAV, which exceeds that of the canine right ventricle. In conclusion, the ES-type chamber provided best pump filling and the B-type chamber best pump ejection, but back pressure at the chamber diaphragm determined performance efficiency. An active filling mechanism for the driving chamber will be necessary to offset the low preload requirements of a VAD, and provide the maximum power output necessary for right ventricular support.
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PMID:Ex vivo performance of muscle powered cardiac assist device: potential for right ventricular support. 180

The need for a better organ preservative solution in heart transplantation is clear. At the same time, newer techniques in the assessment of cardiac function in the laboratory have made accurate load-independent quantification of myocardial preservation possible. Therefore a study was undertaken to evaluate left ventricular function in transplanted hearts after 14 hours of preservation in the intracellular lactobionate solution. Nine dogs were instrumented with ultrasonic dimension transducers, to measure left ventricular epicardial volume, and with micromanometers, to measure left ventricular pressure. Left ventricular wall volumes were determined from epicardial echocardiograms. To define the extent of organ injury resulting from the transplant procedure and cardiopulmonary bypass alone, four other animals were instrumented in a similar fashion, and left ventricular function was assessed after standard cardioplegic arrest and transplantation. The transplant procedures were performed with a warm ischemic period of 0.75 +/- 0.2 hours. In all experiments, data were collected before graft harvest and 1 hour after separation from cardiopulmonary bypass. Standard cardioplegic arrest and 2.4 +/- 0.1 hours of ischemia resulted in a decrease in left ventricular ejection fraction from 0.43 +/- 0.04 to 0.27 +/- 0.1 (37%) (p less than 0.01), a decrease in the slope of the stroke work/end-diastolic volume relationship from 15.4 +/- 7.9 to 7.9 +/- 2.0 erg X 10(4) (49%; p less than 0.01), and a decrease in the myocardial power output from 19.7 +/- 10.9 to 5.9 +/- 1.9 (70%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of myocardial function in orthotopic cardiac allografts after prolonged storage in UW solution. 191 95

The direct effects of desflurane on myocardial contractility in vivo have not been characterized. Therefore, the purpose of this investigation was to systematically examine the effects of desflurane on myocardial contractile function and compare these actions to equianesthetic concentrations of isoflurane in chronically instrumented dogs. Contractility was evaluated using an established index of inotropic state, the preload recruitable stroke work (PRSW) versus end-diastolic segment length (EDL) relationship. Since autonomic nervous system tone may influence the hemodynamic effects of the volatile anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments were performed with seven dogs instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. After autonomic nervous system blockade, ventricular pressure-segment length loops were generated using preload reduction via partial inferior vena caval occlusion. The PRSW versus EDL relation was calculated from the pressure-length loops. Dogs were then anesthetized with 1.0 or 1.5 MAC desflurane or isoflurane in a random fashion, and measurements were repeated after 30 min of equilibration at each anesthetic concentration. The PRSW versus EDL slope reflected similar changes in contractile state when desflurane or isoflurane was administered (53 +/- 4 during control to 26 +/- 4 erg.cm-2 x 10(-3).mm-1 at 1.5 MAC desflurane, and 57 +/- 5 during control to 31 +/- 3 erg.cm-2 x 10(-2).mm-1 at 1.5 MAC isoflurane). In conclusion, desflurane and isoflurane produced equivalent direct decreases in myocardial contractility.
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PMID:Influence of volatile anesthetics on myocardial contractility in vivo: desflurane versus isoflurane. 202 Dec 8

Assessment of the effects of nitrous oxide on myocardial contractile function in vivo has been complicated by lack of a reliable, easily quantified, load-independent index of contractility and by the presence of intact autonomic nervous system reflexes. Although several previous investigations in humans and experimental animals have demonstrated that nitrous oxide possesses direct negative inotropic effects, this conclusion remains controversial. This investigation reexamined the effect of nitrous oxide on myocardial contractile function when this agent was combined with baseline isoflurane or sufentanil anesthesia in chronically instrumented dogs. Contractility was evaluated with the use of the regional preload recruitable stroke work (PRSW)-end-diastolic segment length relationship, a method that provides an accurate, relatively afterload-independent assessment of inotropic state in conscious and anesthetized dogs. Because autonomic nervous system tone may influence the response of systemic hemodynamics to anesthesia in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments, consisting of a total of 15 experiments, were performed with 12 dogs. Dogs, chronically instrumented for measurement of systemic hemodynamics, including left ventricular pressure and subendocardial segment length, were anesthetized with isoflurane or sufentanil. Thirty percent and 70% nitrous oxide were then administered in a random fashion. Left ventricular pressure-segment length loops were generated after 30 min of equilibration after each anesthetic intervention with the use of preload reduction by partial inferior vena caval constriction, and regional PRSW was calculated. Regional PRSW versus end-diastolic length slope reflected decreases in contractile state when nitrous oxide was added to isoflurane (50 +/- 5 for isoflurane alone to 28 +/- 2 erg.cm-2 x 10(-3).min-1 with 70% added nitrous oxide) or sufentanil (73 +/- 8 for sufentanil alone to 52 +/- 5 erg.cm-2 x 10(-3).mm-1 with 70% added nitrous oxide). Similar decreases in left ventricular positive dP/dt50 were observed as well, reflecting decreases in contractile function. The results further suggest that the degree of functional depression produced by nitrous oxide is nearly equal when isoflurane and sufentanil groups are compared. This study demonstrates that nitrous oxide possesses direct negative inotropic actions independent of changes in autonomic nervous system tone in the chronically instrumented dog.
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PMID:Effects of nitrous oxide on myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs. 214 68

This study aimed to evaluate the change in external work and its control mechanism in the concentric hypertrophied heart induced by systemic hypertension. The calculated stroke work, myocardial contractility, afterload, and preload were examined in the baseline period (Control Stage, CS) and in the eighth week after the induction of perinephritic hypertension (Hypertensive Stage, HS) in unanesthetized dogs. These variables were examined with echocardiograms and high-fidelity left ventricular (LV) and ascending aortic pressures. Mean aortic pressure was significantly (p less than 0.05) elevated from 95 +/- 10 to 134 +/- 27 mmHg in HS. The ratio of end-diastolic wall thickness to radius significantly (p less than 0.05) increased in the HS. The calculated stroke work of the LV chamber was significantly (p less than 0.05) increased from 7022 +/- 1203 to 8860 +/- 1548 X 10(3) erg in HS while the stroke work normalized for wall thickness by calculating the wall stress was not altered (3069 +/- 1086 v.s. 2989 +/- 866 erg; CS v.s. HS) with no significant change in heart rate in HS. In the HS, the end-systolic wall stress (afterload) and the slope of end-systolic wall stress-dimension relationship (myocardial contractility) were unchanged while the end-diastolic wall stress (preload) slightly reduced. These results suggest that, in the concentric hypertrophied left ventricle induced by systemic hypertension, the LV myocardial external work is normal, whereas the LV chamber external work increases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of external work of concentric hypertrophied left ventricles in unanesthetized hypertensive dogs. 214 72

A muscle powered cardiac assist device (MCAD) for right ventricular support requires optimized diastolic filling to obtain full stroke and acceptable fluid dynamics. A valved and spring-assembled skeletal muscle ventricle (SMV) was designed as a prototype MCAD, regardless of fluid dynamics. The present study addresses the optimal bypass method for right ventricular support, and predicts the future design for an implantable MCAD. Latissimus dorsi muscle (LDM) of 11 dogs were conditioned electrically for a one year maximum, and transformed into fatigue-resistant muscles (Type I fibers). Superior and inferior vena cavae were anastomosed using one arm of a Y-shaped vascular graft, as an inflow conduit, and the outflow conduit was placed on the main pulmonary artery. SMV was wrapped with transformed LDM and the bypass method was varied by SVC and/or IVC ligation. SMV demonstrated sufficient right ventricular support on total bypass (70% compared with control output), and the maximum pump off-to-on flow ratio (200%) was obtained. Maximum SMV power output was 0.27 X 10(6) erg, which was equivalent to that of canine right ventricle. Right atrial-to-pulmonary artery bypass was also constructed by using SMV in another 14 dogs, and also showed that total bypass was preferable for optimal SMV diastolic filling. In conclusion, specific requirements for a future MCAD include a subsystem assembly such as a spring, magnet, or alternative auxiliary muscle pump assembly for MCAD filling, and total bypass with optimized fluid dynamics and anatomic fitting.
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PMID:A muscle powered cardiac assist device for right ventricular support: total assist or partial assist? 225 2


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