[Extracorporeal circulation and cardiopulmonary bypass].

Modern extracorporeal circulation is state of the art in science and technology. Development of cardiovascular surgery is based on the progress of extracorporeal circulation. If an accident occurs in extracorporeal circulation during a surgical procedure, the patient may suffer a severe injury of his vital organs. Safety management is essential in the operation of extracorporeal circulation for the repair of cardiovascular diseases. Standard manuals of safety management of cardiopulmonary bypass system has recently published by the Japan Society of Extracorporeal Circulation. Collaboration between surgeons and perfusionists is important to develop better cardiopulmonary bypass system and to keep the safety management at high level in cardiovascular surgery.

Incident-simulating device with wireless control for extracorporeal circulation crisis management drills.

Incidents during extracorporeal circulation (ECC) may lead to serious consequences, and troubleshooting exercises are becoming more important. We developed an incident-simulation device operated by remote control for ECC crisis management drills, and evaluated its efficacy at a seminar for perfusionists. This compact device consists of a transmitter and a receiving system and is run by dry batteries without a personal computer. A 4-channel radio-control system is used as the transmitter, and four servomotors placed in a box as the receiving system. To simulate occlusion of 3/8" arterial and venous lines, two servomotors with a rod rotate and the rod compresses the tube. The tilt angle of the stick and the servomotor rotation are in proportion, so that the degree of occlusion is controlled. As a result, the tube lumen becomes "stenotic" and then occluded, depending on the rotation. To cut off the power, the other two servomotors, with a relay system, work as a breaker. When the rod of the servomotor rotates, a micro-switch is turned off. The present device is able to increase perfusion pressure quickly and to simulate inadequate venous drainage quietly. At a seminar for perfusionists, an instructor manipulated the transmitter to create incidents and the participants handled the events effectively. In conclusion, incidents created by this device were perceived as similar to real ECC crises and this device may be useful and educationally effective when used in crisis management drills for perfusionists and trainees.

[Safety measures of extracorporeal circulation by heart surgeons and perfusionists].

In the past, heart surgeons often set up the extracorporeal circulation (ECC) system, primed the circuit, and operated the ECC in Japan. As works of perfusionists recently became specialized, young Japanese heart surgeons seldom receive education on ECC, and rarely operate ECC. ECC accidents are rare, but once it occurs, even a well experienced perfusionist often becomes too upset to think of the next action, while surgeons at the operative table have little knowledge of the ECC system. Reconsideration of ECC education for heart surgeons is still rare. As a medical team, tragedies such as death and life-threatening complication due to an ECC accident are to be prevented at all costs. At an on-site training session for ECC troubles at the 59th annual meeting of Japanese Association for Thoracic Surgery, the basic ECC operations, recovering procedures after an accident, and the use of safety devices were taught to 30 teams of young heart surgeons and perfusionists as a measure to ensure safety of ECC. A questionnaire survey was conducted at the end and satisfactory results were obtained.

[Utility of Ringer's acetate solution as an intraoperative fluid during cardiovascular surgery with cardiopulmonary bypass].

This study aimed to clarify the difference in the effects of Ringer's acetate (AR) and Ringer's lactate (LR) administration during cardiovascular surgery with cardiopulmonary bypass. We evaluated their effects on intra and postoperative metabolism, liver functions, blood gas and hemodynamic states. Twenty patients were divided into two groups; AR group (n = 10) and LR group (n = 10). Intraoperative serum D-lactate levels in LR group were significantly higher than those in AR group from the beginning of the operation to awakening. Serum acetate levels showed no increase in both groups. The arterial ketone body ratio (AKBR) in AR group was higher than that in LR group, but the difference was not significant. Serum glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP) levels in LR group were significantly higher than those in AR group from the induction of the anesthesia. It has been reported that acetate has a greater vasodialatory effect than lactate. However, our findings indicate no significant difference in hemodynamics between the two groups. These results suggest that AR may be more useful than LR during cardiovascular surgery with cardiopulmonary bypass.

Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.

Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease.

BACKGROUND: Angiotensin may play a pathophysiological role in experimental and human cardiovascular disease. Clinical studies have shown that ACE inhibitors reduce mortality, recurrent myocardial infarction, and ischemic events in patients with left ventricular dysfunction. Animal studies suggest that tissue ACE, particularly within blood vessels, may be an important target. METHODS AND RESULTS: To study tissue ACE in human coronary artery disease and to identify potential mechanisms of ACE inhibitor action, we examined ACE expression immunohistochemically in nonatherosclerotic and diseased human coronary arteries. In nonatherosclerotic arteries, ACE immunoreactivity was found in luminal and adventitial vasa vasorum endothelium. In early- and intermediate-stage atherosclerotic lesions, ACE was detected prominently in regions of fat-laden macrophages and in association with T lymphocytes. In advanced lesions, ACE immunoreactivity was also localized to the endothelium of the microvasculature throughout the plaques. Immunoreactive angiotensin II was also detected in these areas. ACE expression in macrophages was further examined by in vitro experiments with a monocytoid cell line. ACE activity was induced threefold after differentiation of the cells into macrophages and was further increased after stimulation with acetylated LDL. CONCLUSIONS: These observations demonstrate that significant sources of tissue ACE in human atherosclerotic plaques are regions of inflammatory cells, especially areas of clustered macrophages as well as microvessel endothelial cells. These results suggest that ACE accumulation within the plaque may contribute to an increased production of local angiotensin that may participate in the pathobiology of coronary artery disease. Plaque ACE probably is an important target of drug action.

[Selective cerebral perfusion with cold blood for the aortic arch surgery].

In seventeen patients with aortic arch aneurysms including seven emergency cases, the selective cerebral perfusion with cold blood (16 degrees C) was applied for the cerebral protection during the surgical procedure. Fifteen of them (88%) including the patient with the long cerebral perfusion (236 min) recovered perfectly and discharged. The selective cerebral perfusion with cold blood may be one of the safe and reliable methods for the repair of aortic arch aneurysm.

Captopril inhibits endothelin-1 secretion from endothelial cells through bradykinin.

Incubation with captopril, an angiotensin I converting enzyme inhibitor, for 24 hours at concentrations up to 10(-7) M inhibited endothelin-1 secretion by endothelial cells. This inhibition of endothelin-1 secretion was reversed by coincubation with 3 x 10(-3) M NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis. Furthermore, captopril enhanced the production of nitric oxide in endothelial cells, suggesting that enhancement of nitric oxide production participates in captopril-induced inhibition of endothelin-1 secretion. Moreover, in the presence of 10(-6) M D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin, a bradykinin B2 receptor antagonist, captopril did not inhibit but rather stimulated endothelin-1 secretion, whereas bradykinin inhibited endothelin-1 secretion, and this inhibition by bradykinin was reversed by coincubation with NG-nitro-L-arginine. In addition, enhancement of nitric oxide production induced by either captopril or bradykinin was inhibited by D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin. Although 10(-6) M des-Arg9-[Leu8]-bradykinin, a bradykinin B1 receptor antagonist, did not affect nitric oxide production by bradykinin, it enhanced the inhibition of endothelin-1 secretion by bradykinin. Furthermore, 10(-7) M des-Arg9-bradykinin, a bradykinin B1 receptor agonist, stimulated endothelin-1 secretion by endothelial cells. These findings suggest that angiotensin I converting enzyme inhibitor inhibits endothelin-1 secretion by the accumulation of endogenous bradykinin in endothelial cells and that the inhibition of endothelin-1 secretion by bradykinin is mediated via B2 receptors.

Effects of manidipine hydrochloride on proliferation and glycosaminoglycan synthesis of cultured vascular smooth muscle cells.

The effects of manidipine hydrochloride, a calcium channel blocker, on the proliferation and the synthesis of glycosaminoglycans (GAG) in cultured rat aortic vascular smooth muscle cells (VSMC) were studied. Mandipine hydrochloride suppressed the DNA synthesis of VSMC dose dependently at concentrations of more than 10(-8) M. Mandipine hydrochloride 10(-6) M suppressed proliferation of VSMC to 50% of the control value. Manidipine hydrochloride stimulated the synthesis of GAG at concentrations above 10(-11) M. Manidipine hydrochloride 10(-8) M stimulated synthesis of GAG to 450% of control. Our findings suggest that because mandipine hydrochloride suppresses proliferation and stimulates GAG synthesis of VSMC, it may be an anti-arteriosclerotic agent.

In vitro characterization of alpha-adrenergic receptor in rabbit detrusor muscle.

In the isolated detrusor smooth muscle of the rabbit urinary bladder, acetylcholine, prostaglandin (PG) F2 alpha, histamine and methoxamine produced dose-dependent contractions. The order of efficacy was acetylcholine greater than PGF2 alpha greater than histamine greater than methoxamine. Acetylcholine and oxotremorine increased tension remarkably in the rabbit detrusor muscle; and McN-A-343 also developed tension, but with weaker sensitivity and efficacy. The contractile response to acetylcholine was competitively antagonized by atropine (pA2 9.24) and pirenzepine (pA2 6.96), respectively. Histamine and 2-pyridylethylamine caused dose-dependent contractions. On the other hand, dimaprit caused no response in this tissue. Mepyramine (pA2 8.80) competitively antagonized the contraction induced by histamine, whereas cimetidine failed to antagonize the contraction even at a high concentration of 10(-5) M. Norepinephrine, phenylephrine and methoxamine have greater efficacies in the ability to contract than clonidine. R(-)- and S(+)-YM-12617 and YM-12617 (pA2 10.4, 8.31 and 9.75, respectively) and prazosin (pA2 8.13), phentolamine (pA2 7.55) and yohimbine (pA2 6.44) competitively antagonized the contraction elicited by methoxamine. These results suggest that the contraction of rabbit detrusor muscle can be mediated by alpha 1-adrenergic receptors as well as M2-muscarinic and H1-histaminergic receptors and suggest that the contractile force mediated by alpha 1-adrenergic receptor agonist is smaller than those stimulated by the other receptor agonists.

Selectivity and specificity for alpha 1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats.

The selectivity and specificity for alpha 1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examined in pithed, spontaneously hypertensive rats. R(-)-YM-12617 and prazosin (1 mg kg-1 p.o.) produced 360- and 88-fold rightward shifts, respectively, of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 (1 mg kg-1 p.o.) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an alpha 1-adrenoceptor antagonist than S(+)-YM-12617. This potency ratio corresponded to that formed in an in-vitro study. Both R(-)- and S(+)-YM-12617 hardly affected the UK-14304, angiotensin II, vasopressin and isoprenaline dose-response curves. These results suggest that R(-)-YM-12617 exerted selective alpha 1-adrenoceptor blocking activity and its activity was specific for alpha 1-adrenoceptors.