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[Cardiac energetics in hypothermia].

In isolated hearts of rats pumping a fluid against hydrostatic pressure, the effect of cooling to 27 degrees C on the mechanical efficiency (ME) and oxygen consumption (MVO2) of the heart, was studied. The ME was presented by the ratio of the heart work to the total energy expense. The latter was estimated by MVO2 measured by the polarographic method. At 27 degrees C, the ME was increased while the MVO2 of the arrested heart was decreased. MVO2 of the working heart in hypothermia was less than control by the same valve as the MVO2 of the heart arrested in hypothermia was less than MVO2 of the arrested control heart. The increase of the heart ME in hypothermia seems to be due, mainly, to reduced "rest metabolism" of the heart.

Animals↗

Acetylcholine-induced vasoconstrictor response of coronary vessels in rats: a possible contribution of M2 muscarinic receptor activation.

A mechanism by which acetylcholine (ACh) may elicit vasoconstrictor response in coronary vessels was studied in rat hearts perfused at a constant flow rate. In spontaneously beating hearts, bolus injections of ACh and carbachol (CCh) produced biphasic changes in coronary perfusion pressure (CPP): a transient increase at the initial period followed by a sustained decrease. In KCl-arrested hearts, ACh and CCh produced a monophasic increase in CPP, which was attenuated by either removal of endothelial cells by saponin or cyclooxygenase inhibition by diclofenac sodium. In the spontaneously beating heart, ACh-induced vasoconstriction was almost abolished by atropine (0.1 microM) and was markedly attenuated by an M2 antagonist, methoctramine (0.1 microM), but not by an M1 antagonist, pirenzepine (1 microM). Arecaidine propargyl ester (APE), an M2 agonist, produced coronary artery constriction which was attenuated by methoctramine (0.1 microM) but not by pirenzepine (0.1 microM) in both spontaneously beating and KCl-arrested hearts. McN-A-343, an M1 agonist, increased CPP in both beating and KCl-arrested hearts, but to a lesser degree than APE. These results suggest that the release of vasoconstrictor prostaglandins from endothelial cells contributes to the vasoconstrictor response to ACh in perfused rat coronary vessels, and the response to ACh appears to be mediated, in part, via the M2 subtype of muscarinic receptors.

Acetylcholine↗

Protein synthesis in the isolated perfused rat heart. Effects of mechanical work load, diastolic ventricular pressure and coronary pressure on amino acid incorporation and its transmural distribution into left ventricular protein.

The mechanisms involved in hypertrophy of the left ventricle were studied in Langendorff-perfused rat hearts by measuring the ventricular protein synthesis and its transmural distribution and by differentiating between the effects of changes in mechanical work load, intraventricular and coronary pressures. An increase in the aortic pressure from 7.85 kPa (80 cm of water) to 19.6 kPa (200 cm of water) in beating hearts increased phenylalanine incorporation into left ventricular protein from 1.4 to 2.0 mumol/g protein (p less than 0.02) during a two-hour perfusion. The protein synthesis was transmurally evenly distributed. A similar elevation in the perfusion pressure in potassium arrested hearts caused an increase in phenylalanine incorporation from 1.5 to 1.9 mumol/ (p less than 0.05) when the intraventricular pressure was adjusted to zero, indicating that the increase in aortic (coronary) pressure and not the work load per se was the reason for increased protein synthesis. Elevation of the end-diastolic pressure from zero to approximately 2 kPa in beating hearts at an aortic pressure of 7.85 kPa, or from 7.85 kPa to 17.3 kPa in K+-arrested hearts, at an aortic pressure of 19.6 kPa caused a significant reduction in subendocardial protein synthesis, whereas subepicardial phenylalanine incorporation was at most only slightly affected. The energetic parameters, oxygen consumption, output of vasoactive purine compounds and distribution of coronary flow indicate that the increase in protein synthesis via the elevation in aortic pressure was not due to the abolition of partial anoxia, whereas the same parameters indicate that the transmural gradient in protein synthesis observed under certain conditions was due to subendocardial ischemia when the intraventricular pressure approached the aortic pressure in arrested hearts, which are evidently of restricted use for extended periods without special measures to limit the build-up of intraventricular pressure.

Adenosine Triphosphate↗

Influence of pretreatment on interstitial and intracellular space of canine left-ventricular myocardium.

In this study, the interstitial space and myocytes were investigated qualitatively and morphometrically in samples from beating, fibrillating as well as from cardioplegically HTK-arrested hearts fixed by immersion or perfusion. The size of tissue clefts separating bundles of myocytes and that of the interstitial space within bundles of myocytes depend on the functional state and on the kind of fixation. Cellular preservation is significantly better in HTK-arrested hearts compared to beating or fibrillating hearts. Thus, for the structural evaluation of myocytes and interstitium, the pretreatment constitutes a highly significant factor.

Animals↗

Beneficial effects of H290/51, a new lipid peroxidation inhibitor, on functional recovery after ischemia and reperfusion in isolated cold-arrested rat hearts.

Lipid peroxidation is one of the major mechanisms involved in free radical-mediated postischemic myocardial injury. In the present study, a newly synthetized lipid peroxidation inhibitor H290/51 [cis-7methyl-9-methoxy-5,5a,b,10b- tetrahydroindeno(2,1-6 indole)] was evaluated for its effects on myocardial functional recovery during reperfusion after 30-min global ischemia in isolated cold-arrested rat hearts. Administration of 200 and 800 nM H290/51 at initiation of global ischemia markedly improved the functional recovery, whereas 50 nM H290/51 had no significant effects. The percent recovery of cardiac output (CO), left ventricular developed pressure (LVDP), and LVdP/dtmax at the end of the 30-min reperfusion period in the working mode was much higher in the groups receiving 200 and 800 nM H290/51 than that in vehicle group (CO 73 +/- 5 and 60 +/- 5 vs. 23 +/- 7%; LVDP 79 +/- 5 and 73 +/- 8 vs. 43 +/- 10%; LV dP/dtmax 78 +/- 5 and 69 +/- 4 vs. 45 +/- 10%). The indenoindole compound H290/51 reduced ischemia/reperfusion-induced cardiac dysfunction.

Analysis of Variance↗

Evaluation of ascending aortic atherosclerosis with 16-multidetector computed tomography is useful before total endoscopic coronary bypass surgery.

BACKGROUND: The purpose of this study was to investigate the assessment of ascending aortic atherosclerosis with 16-multidetector computed tomography (16-MDCT) angiography prior to total endoscopic coronary artery bypass (TECAB) surgery. METHODS: Forty-five patients were examined with electrocardiogram-gated, 16-MDCT angiography. The presence of atherosclerosis at the ascending aorta was graduated as severe (>50% of circumference) or as mild (<50% of circumference). Ascending aortic plaque composition was evaluated based on CT densities expressed as Hounsfield units (HU). TECABs using the Da Vinci telemanipulator were performed either on the arrested heart (n = 39) with an intra-aortic cardiopulmonary bypass (CPB) perfusion device or on the beating heart (n = 6) in patients with severe atherosclerosis. RESULTS: The presence of mild atherosclerosis at the ascending aorta (11/39) was associated with intra-aortic CPB perfusion device-related difficulties such as intra-aortic balloon migration (BM) or balloon rupture (P = .007) in arrested heart TECABs. The CT density of atherosclerotic plaque in patients with BM was mean 58 HU +/- 51 standard deviation (SD), suggesting noncalcifying plaque. In patients without BM, CT density of plaque was mean 526 HU +/- 306 SD corresponding to calcifying plaque (P < .001). Balloon rupture occurred in 2 patients who had calcifying plaque at the ascending aorta. CONCLUSION: Evaluation of ascending aortic atherosclerosis with 16-MDCT angiography is useful prior to TECAB surgery. Even mild atherosclerosis of the ascending aorta is associated with intraoperative difficulties regarding the remote-access perfusion system that is used for arrested heart TECAB surgery.

Aorta↗

Subendocardial and subepicardial pressure-flow relations in the rat heart in diastolic and systolic arrest.

Ischemic heart disease is more apparent in the subendocardial than in subepicardial layers. We investigated coronary pressure-flow relations in layers of the isolated rat left ventricle, using 15 microm microspheres during diastolic and systolic arrest in the vasodilated coronary circulation. A special cannula allowed for selective determination of left main stem pressure-flow relations. Arterio-venous shunt flow was derived from microspheres in the venous effluent. We quantitatively investigated the pressure-flow relations in diastolic arrest (n=8), systolic arrest at normal contractility (n=8) and low contractility (n=6). In all three groups normal and large ventricular volume was studied. In diastolic arrest, at a perfusion pressure of 90 mmHg, subendocardial flow is larger than subepicardial flow, i.e., the endo/epi ratio is approximately 1.2. In systolic arrest the endo/epi ratio is approximately 0.3, and subendocardial flow and subepicardial flow are approximately 12% and approximately 55% of their values during diastolic arrest. The endo/epi ratio in diastolic arrest decreases with increasing perfusion pressure, while in systole the ratio increases. The slope of the pressure-flow relations, i.e., inverse of resistance, changes by a factor of approximately 5.3 in the subendocardium and by a factor approximately 2.2 in the subepicardium from diastole to systole. Lowering contractility affects subendocardial flow more than subepicardial flow, but both contractility and ventricular volume changes have only a limited effect on both subendocardial and subepicardial flow. The resistance (inverse of slope) of the total left main stem pressure-flow relation changes by a factor of approximately 3.4 from diastolic to systolic arrest. The zero-flow pressure increases from diastole to systole. Thus, coronary perfusion flow in diastolic arrest is larger than systolic arrest, with the largest difference in the subendocardium, as a result of layer dependent increases in vascular resistance and intercept pressure. Shunt flow is larger in diastolic than in systolic arrest, and increases with perfusion pressure. We conclude that changes in contractility and ventricular volume have a smaller effect on pressure-flow relations than diastolic-systolic differences. A synthesis of models accounting for the effect of cardiac contraction on perfusion is suggested.

Animals↗

Vagus nerve stimulation as a method to temporarily slow or arrest the heart.

BACKGROUND: Electrical stimulation of nerves is used to study nervous system and body function relationships. Electrical stimulation of the vagus nerve was used to slow the heart during coronary artery bypass grafting. METHODS: A 48-year-old man with multivessel coronary artery disease, scheduled for revascularization, gave informed consent for the surgeon to stimulate his vagus nerve. As part of the operation the left internal mammary artery was harvested as a pedicle and the patient was placed on cardiopulmonary bypass. The vagus nerve was isolated as it crossed the aorta just lateral to the phrenic nerve. Pacing wires were placed (1 cm apart) allowing prodromic conduction. With the patient fully supported by cardiopulmonary bypass and after administration of neostigmine (2.5 mg intravenously) eight separate continuous 5-second electrical pulse trains (25 Hz, 20 V, pulse width of 0.1 ms) were delivered to the nerve with 30-second rest periods between each stimulation. During the periods of stimulation the mammary artery to left anterior descending artery anastomosis was completed. RESULTS: Electrical stimulation caused cessation of the heartbeat, termination of the same resulted in normal sinus rhythm, although it was slowed by the neostigmine. Suturing of the anastomosis was done during periods of stimulation. Additional anastomoses were completed using cardiopulmonary bypass-delivered cardioplegia and aortic cross-clamping. CONCLUSIONS: Electrical stimulation of the vagus nerve slowed and temporarily arrested the heart for brief periods to allow critical placement of anastomotic sutures.

Adult↗

Assessment of myocardial perfusion with laser Doppler flowmetry. An experimental study on porcine heart.

Laser Doppler flowmetry was applied to the arrested heart of four pigs and to the fibrillating heart of three pigs during cardiopulmonary bypass. The coronary blood flow was maintained during cardiac arrest by infusion of hyperkalemic blood into the aortic root. A significant correlation (r = 0.88, n = 52, p less than 0.001) between laser Doppler signal and coronary blood flow was found during cardiac arrest. During ventricular fibrillation after release of the aortic cross-clamp there was significant correlation (0.84, n = 38, p less than 0.01) between laser Doppler signal and extracorporeal blood flow. A residual laser Doppler signal of about 60% of the maximal value was recorded even after the bypass flow was discontinued. Laser Doppler flowmetry is concluded to permit measurement of myocardial perfusion in the arrested porcine heart. Muscular activity of the heart contributes to the output signal during ventricular fibrillation.

Animals↗

Dynamic changes in three-dimensional architecture and vascular volume of transmural coronary microvasculature between diastolic- and systolic-arrested rat hearts.

BACKGROUND: The phase difference of coronary arterial and venous flows indicates the importance of intramyocardial capacitance vessels in storing diastolic flow and in discharging volume in systole. However, the anatomic and functional characteristics of the capacitance vessels are unclear. We aimed to clarify those characteristics with their transmural difference by 3D visualization of transmural microvessels under diastole and systole. METHODS AND RESULTS: We performed complete intracoronary filling of a contrast medium into Langendorff's Wistar rat hearts under (1) St Thomas-perfused diastolic arrest (D-mode) and (2) BaCl(2)-induced systolic arrest (S-mode). Precise transmural 3D architectures of capillaries and of pre- and post-capillary microvessels (ie, microvessels larger than capillaries) were visualized clearly with a confocal laser scanning microscope and x-ray microcomputed tomography (microCT), respectively. Vascular volume fraction (VF) and systolic-induced VF reduction rate from D- to S-mode were analyzed. The net capillary VF in D-mode (20.4 +/- 0.9%) was 10 times that of larger microvessels and was reduced in S-mode by 32% without capillary collapse. Systolic-induced VF reduction rate was smaller in capillaries than in larger microvessels (48%; P<0.05). The larger microvessel VF in D-mode (2.2 +/-0.2%) was reduced in S-mode, accompanied by complicated 3D deformation. CONCLUSIONS: Capillaries were relatively resistant to the systolic extravascular compression compared with pre- and post-capillary microvessels, conveniently beneficial for the myocardial oxygen delivery throughout a cardiac cycle. Nevertheless, a larger change in the absolute volume of capillaries may function as effective capacitance. On one hand, the pre- and post-capillary microvessels showed a larger phasic change in resistance, which may function to maintain the capillary patency during systole.

Animals↗

[Cadaver donor nephrectomy. Surgical technique in the context of multi-organ donation].

95% of renal transplantations performed in France use cadaver donor kidneys. Two donor nephrectomy techniques are proposed: a beating heart technique and an arrested heart technique. In the very great majority of cases (80%), donor nephrectomy can be performed during multi-organ removal, performed according to bioethical regulations: unrelated, anonymity between donor and recipient, security, traceability and evaluation. The urologist has a role to play at each step of organ donation, in which he is the main protagonist. The first steps are performed in close collaboration with the intensive care unit which established the diagnosis of brain death of the potential donor. The following steps, guided by the French transplant establishment, are the urologist's responsibility: He is responsible for abdominal exploration looking for a tumour or any other abnormality. A strictly aseptic technique is essential to prevent contamination of the organ. He is responsible for removing kidneys in such a way as to ensure the shortest possible warm ischaemia time, the best storage solution, and the best preservation of their anatomical structure. He must be familiar with the outcome of transplants in order to adapt his technique to the results of transplants.

Brain Death↗

[Intermittent warm blood cardioplegia--an experimental study].

The influence of intermittent warm blood cardioplegia (WBCP) on myocardial function and metabolism was studied. Fourty-two adult mongrel dogs were used. The isolated heart of one dog was perfused by the cross circulation method with another support dog. The dogs then were divided into three groups. In group I (n = 6), the empty beating heart was perfused with warm blood (WB) kept at 36 degrees C for 100 minutes. In group II (n = 7), the arrested heart was perfused with continuous WBCP using modified Fremes solution for 100 minutes. In group III (n = 8), the arrested heart was perfused with WBCP for 10 minutes following a 15-minute non-perfusion period. This perfusion method was repeated four times. The E max, LV developed pressure, +/- LV dp/dt and LVEDP were all measured to evaluated the myocardial function. In addition, the coronary venous blood pH, myocardial oxygen consumption, myocardial lactate extraction, coronary blood flow, myocardial high energy phosphate content and myocardial water content were also studied in order to elucidate the myocardial metabolism. Regarding the myocardial function, no significant difference was observed between the three groups. The results of chemical studies on the myocardial metabolism were as follows: (1) the coronary venous blood pH in group III decreased at the end of the no perfusion period of WBCP. But it thereafter gradually returned to the normal physiological range; (2) the myocardial oxygen consumption in group III increased just after each interruption, but then gradually decreased toward following intermittent WBCP; (3) the myocardial lactate extraction decreased at the end of the non-perfusion period. However, it gradually returned to the control value by the end of each period of WBCP perfusion; (4) after 60 minutes of reperfusion, the coronary venous blood pH, myocardial oxygen consumption and myocardial lactate extraction showed no significant differences between the groups; (5) the coronary blood flow in group III increased significantly after 1 minute of reperfusion; (6) the ATP value in group III decreased significantly after 60 minutes of reperfusion. The ADP and AMP values demonstrated no significant difference between the groups during the same period; and (7) no significant difference was seen in the myocardial water content between the groups after 60 minutes of reperfusion. It is thus concluded that 10 minutes of intermittent WBCP followed by a 15-minute interruption appeared to have no deleterious effect on the myocardial function and metabolism.

Animals↗

[Knowledge, attitudes and behavior regarding organ transplantation: the impact of the first transplantation from a brain-dead donor under the organ transplantation act].

OBJECTIVE: To investigate knowledge, attitudes and behavior regarding organ transplantation, and to estimate the impact of the first organ transplantation from a brain-dead donor under the Organ Transplantation Act. SUBJECTS AND METHODS: A telephone survey was made using the Random Digit Dialing method in May 1999. People living in the Tokyo Metropolitan area ages 20 years or over were asked about their knowledge, attitudes and behavior regarding organ transplantation, and their opinions on the first organ transplantation conduced in February 1999. The results were compared with an opinion poll made 7 months previously to estimate the impact of this first case. RESULTS: The number of respondents was 489 (response rate: 46.0%). 1) Knowledge of organ transplantation: most people knew that organ donation from brain-dead donors was possible under the act, and that written consent on a form and family member's agreement were necessary before donating. More people knew about donor cards. 2) Organ transplantation: more people were willing to donate their organs when they die, and to agree to donation when a family member died who had wanted to donate his/her organs on their death. In the poll 7 months before, fewer people were willing to donate their organs or to agree to donate their family member's organs after brain death compared with after heart arrest. However, no such difference between brain death and heart arrest was found in this later study, suggesting that the distinction between the two was no longer considered to be so important. 3) Respondents themselves having donor cards constituted 15.2%, showing a marked increase from 7 months earlier. Another 39.7% wished to carry a donor card; the most common reason for not carrying one was they did not know how to acquire it. 4) The first transplantation was considered to have contributed to the increase in knowledge, and a favorable change in attitudes and behavior toward organ transplantation. 5) Respondents who agreed to that organ donation from children aged under 15 should be possible constituted 46.4%, of the to be this not being allowed at the present time. 6) The majority of respondents considered that the brain death was diagnosed properly in the first case and that the donation was made voluntarily, concluding that the transplantation was made fairly. 7) Respondents who considered that the privacy of the donor and the recipients was violated were 46.2% and 36.1%, respectively. The attitude of the mass media toward the first transplantation was criticized by 56.9% of the respondents. 8) Respondents who had a favorable impression of the organ transplantation were 61.9%. Such people are likely to donate their organs, to agree to a family member's donation, and to have a donor card than people who had not gained a favorable impression. The two groups exhibited no difference in their knowledge concerning organ transplantation. CONCLUSIONS: An increase in knowledge and a favorable change in attitudes and behavior regarding organ transplantation was confirmed in this survey, as compared with results 7 months earlier, probably because the first transplantation took place. The majority of the respondents considered that the first transplantation was made fairly, although they criticized the attitude of the mass media invading the privacy of the donor and the recipients. Further studies should be made to facilitate effective delivery of donor cards to people who want to carry them, and to change the rules on organ donation from children.

Adult↗