Effects of profound hemodilution on small-intestinal wound healing in rabbits.

BACKGROUND: Wound healing is influenced by tissue oxygen tension and blood perfusion, but not by moderate anemia or hemodilution. The effect of perioperative profound hemodilution on small-intestinal wound healing remains unclear. METHODS: We performed jejunectomy followed by end-to-end anastomosis in rabbits subjected to a variety of perioperative hemodilutions: HD((HES)), hemodiluted with hydroxyethylstarch; HD((P+HES)), hemodiluted with autologous plasma and hydroxyethylstarch; HD((HES))/R, hemodiluted with hydroxyethylstarch and retransfused afterward. Intraoperative hemoglobin levels were 5 g 100 ml(-1). On Postoperative Day 5, the tensile strength (TS) of the anastomosis was measured and histological specimen was obtained. The time courses of hemoglobin, serum albumin (Alb), plasma fibrinogen (Fbg), and plasma activity of factor XIII (F XIII) were measured. RESULTS: TS in HD((HES))/R (236.0 +/- 52.2 gf) was similar to that in control (266.5 +/- 41.6 gf); however, TS in HD((HES)) (179.8 +/- 17.9 gf) and HD((P+HES)) (165.5 +/- 14.7 gf) decreased significantly. The histological findings in HD((HES))/R were similar to those of control, whereas they demonstrated a delayed healing process in HD((HES)) and HD((P+HES)). Hemoglobin levels were still lower on Postoperative Day 5 in HD((HES)) and HD((P+HES)), but increased to 10.0 g 100 ml(-1) after retransfusion in HD((HES))/R. Hemodilution caused significant decreases in Alb, Fbg, and F XIII, but the values after retransfusion in HD((HES))/R were similar to postoperative values in HD((P+HES)). CONCLUSION: Intraoperative profound hemodilution does not interfere with small-intestinal wound healing as long as postoperative hemoglobin levels were maintained above 10 g 100 ml(-1). Postoperative levels of other plasma constituents may not influence wound healing.

[Anesthetic management of patients with malignant pleural effusion undergoing hyperthermic perfusion under thoracoscopy].

Nine patients with malignant pleural effusion due to lung cancer had been scheduled for hyperthermic treatment with warmed distilled water (40 degrees C) under thoracoscopy. This treatment aims to produce adhesion of the lungs to reduce pleural effusion. To evaluate the risk of general anesthesia for patients with lung cancer at the end stage, we examined the problems of perioperative management. Seven out of nine patients were classified into ASA physical status > or = III and seven patients into Hugh Jones > or = III Shapiro's score was > or = 5 in four patients. The average %VC was 60 +/- 16 and % FEV1.0 was 41 +/- 18% (means +/- SE). A double lumen endotracheal tube was inserted and anesthesia was maintained with inhalational anesthetics. In two cases, one-lung ventilation could not be maintained because of severe hypoxemia during hyperthermic perfusion. Hypertension occurred in three cases and hypotension in one by direct heat stimulation of the cardiopulmonary system. Although their preoperative risk was poor, there were no major complications and the quality of life was improved. We stress that careful anesthetic management is important for avoiding hypoxemia and hemodynamic instability during this treatment.

Comparison of the effects of pancuronium and vecuronium in canine coronary and renal arteries.

BACKGROUND: Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done to determine the actions and mechanisms of action of pancuronium on coronary and renal arteries other than those as a sympathomimetic agent. METHODS: Helical strips of coronary and renal arteries from mongrel dogs were suspended in oxygenated, warmed Ringer-Locke solution, and changes in the isometric tension were recorded. In some strips, transmural electrical stimulation (5 Hz for 40 s) was applied to activate perivascular adrenergic nerves. RESULTS: Pancuronium (10[-7] to 10[-5] M) caused dose-dependent relaxation in coronary and renal arteries contracted with prostaglandin (PG) F2alpha, whereas no significant response was induced with vecuronium. The relaxation was endothelium independent and abolished by indomethacin or tranylcypromine, a PGI2 synthase inhibitor. Transmural electrical stimulation caused coronary arterial relaxation, which was augmented by pancuronium and vecuronium. Desipramine also increased the response, and additional potentiation of the response was not elicited by pancuronium and vecuronium. In renal arteries, electrical stimulation caused contraction, which was also augmented by pancuronium and vecuronium. With desipramine treatment, these muscle relaxants did not potentiate the response. Endothelium-dependent coronary arterial relaxation caused by bradykinin was not affected by pancuronium. CONCLUSIONS: Pancuronium-induced relaxations in canine coronary and renal arteries appear to be mediated by PGI2 released from subendothelial tissues. Potentiations by pancuronium and vecuronium of the response to adrenergic nerve stimulation are expected to be due to an inhibition of the norepinephrine uptake but not to facilitated release of the amine.

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

BACKGROUND: The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. METHODS: Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. RESULTS: The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. CONCLUSIONS: These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

The effects of halothane and isoflurane on the phosphoenergetic state of the liver during hemorrhagic shock in rats: an in vivo 31P nuclear magnetic resonance spectroscopic study.

We studied the effects of halothane versus isoflurane on the phosphoenergetic state and intracellular pH (pHi) of the rat liver using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy during and after hemorrhagic shock. Seventeen rats were anesthetized with 1 minimum alveolar anesthetic concentration of halothane or isoflurane. The mean arterial blood pressure was reduced to 40 mm Hg and maintained at this level for 45 min by withdrawing blood from the common carotid artery. The shed blood was then returned slowly. In vivo 31P NMR spectra were consecutively collected throughout the study. The phosphoenergetic state of the liver was evaluated from the changes in adenosine triphosphate (ATP) and inorganic phosphate (P(i)) levels. pHi was calculated from the chemical shifts of P(i) and alpha-ATP peaks. During hemorrhagic shock, beta-ATP decreased to 35% and 45%, and P(i) increased to 300% and 230% of their initial values in the halothane and isoflurane groups, respectively. Intracellular acidosis was more severe in the halothane group. The recoveries of beta-ATP and P(i) were better in the isoflurane group. Halothane showed a more detrimental effect than isoflurane on the hepatic phosphoenergetic level during and after hemorrhagic shock.

The effects of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids on the recovery of cardiac function following cold preservation and reperfusion in hyperlipidemic rats.

We examined the effects of supplementation with eiosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids (PUFAs), on basal cardiac function and recovery of cardiac function of "donor hearts" from adults (30 week) rats following cold preservation and reperfusion (P/R). In groups 1, 2, 3, and 4, respectively, 30-week-old rats were fed a soybean oil diet, a high-cholesterol oil (HC) diet, an HC diet with EPA, or an HC diet with DHA for 5 weeks. After collecting blood to analyze plasma levels of fatty acids among each group, the heart was excised and perfused on a Langendorff apparatus. Following evaluation of each rat's cardiac function, each heart was stored in HTK solution for 8 hr at 4 degrees C. The heart was then reperfused and the coronary perfusate was collected to evaluate enzyme that had leaked. After cardiac functional recovery was estimated, myocardial fatty acids were measured. EPA supplementation significantly increases the plasma and cardiac levels of EPA as well as the ratio of EPA to arachidonic acid (AA). EPA supplementation also led to improved recovery of cardiac function following P/P, compared with that of rats who received soybean oil, high-cholesterol oil, and DHA. DHA supplementation significantly increased the plasma and cardiac levels of DHA as well as the ratio of DHA to AA--however, the cardiac functional recovery was almost identical to that of the rats who received high-cholesterol oil and was higher only than that of the rats who received soybean oil. There were no significant differences in enzyme that had leaked and myocardial water content among each group. These results suggest that alterations in the myocardial phospholipid composition by EPA supplementation may be profoundly responsible for attenuating myocardial I/R injuries. In contrast, DHA supplementation may not exert a cardioprotective effect following cold P/R. DHA supplementation alone may not increase the myocardial level of EPA enough to cause a protective effect against P/R injury. EPA supplementation to hyperlipidemic patients may be clinically warranted for increasing the potential number of donors.

Arterial baroreflex inhibition by midbrain periaqueductal grey in anaesthetized rats.

Midbrain periaqueductal grey (PAG) provokes the defense reaction when stimulated. The present study was conducted to determine whether, and how, the PAG produces baroreflex inhibition, a feature characterizing the hypothalamic defense reaction. In chloralose-urethane anaesthetized rats, baroreflex vagal bradycardia and baroreflex hypotension were provoked by aortic depressor nerve stimulation. When the PAG was electrically stimulated baroreflex vagal bradycardia was remarkably suppressed; suppression of baroreflex hypotension was observed following bilateral vagotomy. In contrast, chemical stimulation of the PAG by D,L-homocysteic acid microinjection markedly suppressed baroreflex vagal bradycardia but only minimally suppressed baroreflex hypotension. These findings suggest that whereas overall PAG stimulation inhibits not only cardiac but also vascular components of baroreflexes, inhibition of the latter component either depends largely on activation of passing fibers or requires recruitment of a larger number of PAG cell bodies. PAG inhibition of baroreflex vagal bradycardia was not affected following spinal cord transection at C1, indicating that the inhibition was exclusively central in origin and not due to peripheral, prejunctional inhibition of vagal acetylcholine release by increased cardiac sympathetic nerve activities. The PAG inhibition of baroreflexes was greatly attenuated following electrolytic as well as chemical destruction of the parabrachial region. On the other hand, when the PAG was extensively lesioned, baroreflex inhibition produced by hypothalamic defense area stimulation was markedly diminished. PAG excitation thus causes powerful inhibition of arterial baroreflexes which is mediated by the parabrachial region; the PAG also mediates a major fraction of hypothalamic inhibition of the baroreflexes.

Somatosensory and hypothalamic inhibitions of baroreflex vagal bradycardia in rats.

Somatosensory and forebrain mechanisms inhibiting arterial baroreflexes were investigated in chloralose-urethane anesthetized and artificially ventilated rats. Electrical stimulation of the sciatic nerve (ScN) and the hypothalamic pressor area (HP) suppressed baroreflex vagal bradycardia (BVB) and hypotension provoked by electrical stimulation of the aortic depressor nerve (ADN). Suppression of BVB was more marked, but inhibitory potencies of ScN and HP were not different. These two inhibitions were considered to have a functional implication in common, since both were accompanied by increase in hindlimb vascular conductance. A variety of experiments were conducted to localize the target site of ScN and HP inhibitions of BVB. Either ScN or HP stimulations was without effect on antidromic compound spike potentials along ADN evoked by microstimulation of the nucleus tractus solitarius (NTS), precluding the possibility of these inhibitions being presynaptic. Both ScN and HP stimulation suppressed ADN-induced field potentials in the NA region which provoked vagal bradycardia upon microstimulation, but failed to affect ADN-induced responses, either field or unitary, in the NTS region. Antidromic unitary responses in the NA region to vagus cardiac branch stimulation were suppressed by ScN and HP stimulations in NTS-lesioned rats. Intracisternal bicuculline, a GABA antagonist, was found to abolish both ScN and HP inhibitions of BVB, while intracisternal muscimol, a GABA agonist, eliminated bradycardia. These findings suggest that somatosensory and forebrain inhibition of BVB occur principally at the preganglionic cell level and are probably mediated by a GABAergic mechanism.

Solitary nucleus neurons transmitting vagal visceral input to the forebrain via a direct pathway in rats.

Electrical stimulation of the hypothalamus in rats anesthetized with chloralose-urethane evoked antidromic responses in 5% of the neurons in the nucleus tractus solitarius (NTS) which responded orthodromically to vagus nerve stimulation. The NTS neurons with such a direct forebrain projection (F-NTS neurons) were distributed mostly in the lateral part of the ipsilateral commissural NTS. Latencies of the antidromic responses ranged from 20 to 75 ms, indicating that the axons of the F-NTS neurons were unmyelinated. Orthodromic responses (latencies, 20 to 80 ms) were observed in 6 of 23 F-NTS neurons, to the same stimuli that evoked the antidromic responses. Sites that elicited antidromic responses in the F-NTS neurons upon stimulation covered almost all medial hypothalamic nuclei, but 65% were localized in the preoptic-anterior hypothalamic region. All orthodromic responses to activation of vagal afferent fibers (either myelinated or unmyelinated) were polysynaptic in nature. Three F-NTS neurons were found to project to two different hypothalamic regions, by axonal branching. In addition, the firing rate of most F-NTS neurons was not appreciably affected by norepinephrine-induced blood pressure increase. It is concluded that vagal visceral input is transmitted polysynaptically to the F-NTS neurons and is then conveyed to the forebrain via the direct pathway.