The effect of Des-Arg9-bradykinin and bradykinin-potentiating peptide C on isolated rat hearts.

OBJECTIVES: Des-Arg9-bradykinin and bradykinin-potentiating peptide C (BPPC) may contribute to the regulation of cardiovascular function. Therefore, we studied effects of these peptides on coronary perfusion pressure (CPP), heart rate, left ventricular developed pressure (LVDP) and maximum rate of increase of left ventricular pressure (+dP/dtmax). METHODS: The isolated rat hearts were perfused with modified Krebs-Henseleit solution. RESULTS: Infusion of 10, 100 and 1000 nM Des-Arg9-bradykinin decreased CPP (-13.6, -14.8 and -19.0%), LVDP (-16.5, -21.0 and -30.7%) and +dP/dtmax (-11.8, -17.8 and -23.7%), respectively (p < 0.001). Ten or 100 nM Des-Arg9-bradykinin did not alter heart rate, but 1000 nM increased it (+11.3%, p < 0.01). One, 10 and 100 nM BBPC reduced CPP (-16.3, -28.5 and -47.5%), LVDP (-12.6, -19.6 and -21.3%) and +dP/dtmax (-8.7, -18.6 and -20.3%), respectively (p < 0.001). BPPC increased heart rate at 1 nM (+9.6%, p < 0.05 ) and at 10 nM (+14.2%, p < 0.01), however 100 nM decreased it (-15.3%, p < 0.001). CONCLUSIONS: This study evidences that Des-Arg9-bradykinin and BPPC possess vasodilatory effect with modest negative inotropic action. Furthermore, high-dose of Des-Arg9-bradykinin and low-dose of BPPC may produce a tachycardic action, but high dose of BBPC may cause a bradycardic action.

Effects of sleep deprivation on cardiorespiratory functions of the runners and volleyball players during rest and exercise.

The effect of sleep deprivation on male runners (age 18.1 +/- 0.35) and volleyball players (age 17.8 +/- 0.36) has not been investigated. Therefore, we studied the possible effect of sleep deprivation in the sportsmen. The athletes performed spirometric tests at rest and then incremental exercise test on ergometer following one night sleep and one night (25-30 h) sleeplessness. Several standard measurements of spirometric function showed no significant change following sleep loss. Sleep loss raised resting oxygen uptake (VO2) in the runners and resting carbon dioxide production (VCO2) in both the runners and the volleyball players (p < 0.05). However, it left heart rate (HR), respiratory quotient (R), minute ventilation (VE) and arterial oxygen saturation (SaO2) unchanged at rest in both groups. Sleep loss decreased time to exhaustion in the volleyball players (p < 0.01). In the runners and the volleyball players, sleep loss did not alter exercise values of HR, VO2, VCO2, R and SaO2, but it reduced exercise VE (p < 0.05). We suggest that one night sleep deprivation may reduce exercise performance by decreasing exercise VE and time to exhaustion. We also indicate that sleep loss may decrease more the performance of volleyball players than that of runners.

Cardioprotection with resveratrol pretreatment: improved beneficial effects over standard treatment in rat hearts after global ischemia.

OBJECTIVE: The major objective of the present study is to evaluate the potential role of resveratrol (RVT), a natural antioxidant found in grapes and red wine, in protecting the myocardium from the deleterious effects of ischemia-reperfusion (I/R) injury using isolated rat hearts. METHODS: Langendorff perfused isolated rat hearts were subjected to 60 min of global ischemia following 60 min of reperfusion. RVT was given according to chronic pretreatment and/or acute treatment protocols. Animals received RVT at the dose of 20 mg/kg via an intragastric tube for 14 days before the experiment and/or at the infusion concentration of 10 microM for 30 min before the onset of ischemia. The myocardial postischemic recovery was compared using hemodynamic data (peak systolic pressure, end diastolic pressure, and +dP/dtmax), coronary flow, biochemical parameters (LDH, CK-MB, cTnI, myoglobin) from coronary effluent, and oxidative stress markers (MDA, GSH, carbonyl) from heart tissue homogenates in each group. RESULTS: RVT pretreatment and treatment protocols have provided increased preservation in myocardial recovery following global ischemia compared to a non-treated group. Furthermore, the ischemic damage of myocardium was significantly lower in chronic pretreated rats than in the acutely treated group. In contrast, no significant difference was observed in cardioprotective effects of RVT between the only pretreated group, and both the pretreated and treated group throughout reperfusion. CONCLUSION: The findings from this study indicate that RVT has potent cardioprotective properties against I/R injury in rat hearts. The study also highlighted that the administration of RVT, as pretreatment, has amplified the beneficial effects over the standard treatment.

Subcutaneous emphysema following severe vomiting after emerging from general anesthesia.

Postoperative nausea and vomiting-related subcutaneous emphysema is an unexpected complication, especially after uneventful surgery and anesthesia. Here we report and discuss two cases of subcutaneous emphysema following severe retching and vomiting which resolved spontaneously after several days.

The effect of adrenomedullin, amylin fragment 8-37 and calcitonin gene-related peptide on contractile force, heart rate and coronary perfusion pressure in isolated rat hearts.

The effect of human adrenomedullin, human amylin fragment 8-37 (amylin 8-37) and rat calcitonin gene-related peptide (CGRP) on contractile force, heart rate and coronary perfusion pressure has been investigated in the isolated perfused rat hearts. Adrenomedullin (2x10(-10), 2x10(-9) and 2x10(-8) M) produced a significant decrease in contractile force and perfusion pressure, but only the peptide caused a decline in heart rate at the highest dose. Amylin (10(-9), 10(-8) and 10(-7) M) significantly increased and then decreased contractile force. Two doses of amylin (10(-8) and 10(-7) M) induced a significant increase in heart rate, however amylin did not change perfusion pressure in all the doses used. Rat alpha CGRP (10(-8), 10(-7) and 10(-6) M) evoked a slight decline in contractile force following a significant increase in contractile force induced by the peptide. CGRP in all the doses raised heart rate and lowered perfusion pressure. Our results suggest that adrenomedullin has negative inotropic, negative chronotropic and coronary vasodilator actions. Amylin produces a biphasic inotropic effect and evokes a positive chronotropy. CGRP causes positive inotropic, positive chronotropic and vasodilatory effects in isolated rat hearts.

Lidocaine-containing Euro-Collins solution prevents renal injury in the isolated perfused canine kidney exposed to prolonged cold ischemia.

Previous studies have reported a decreased incidence of delayed graft function after cadaveric transplantation with the use of lidocaine pretreatment of the donor. We evaluated the effects of lidocaine on prolonged cold ischemia and reperfusion injury in a canine model of isolated kidney perfusion (IPK). The purpose of this study was to evaluate the renal function of isolated perfused canine kidneys after 48 h of cold storage with Euro-Collins (EC) solution or EC solution plus lidocaine. Isolated perfused canine kidneys were randomized into four groups which contained six kidneys: I) cold flush with EC solution and immediately reperfused, II) cold flush with EC solution plus lidocaine and immediately reperfused, III) 48 h of cold storage with EC and reperfusion, IV) 48 h of cold storage with EC solution plus lidocaine and reperfusion. The measured renal functions were glomerular filtration rate, urine production, perfusate flow, urinary lactic dehydrogenase (ULDH), Na reabsorptive capacity, and tissue MDA levels. Histological examination was performed after reperfusion. The tubular functions of kidneys preserved with EC solution containing lidocaine were better when compared with the kidneys preserved with EC alone. Tubular injury marker levels (ULDH) in group IV were significantly lower than in group III and lidocaine also reduced lipid peroxidation during reperfusion. This is in agreement with the histological results. The results of the present study can be taken as evidence of the cytoprotective effect of lidocaine, which may therefore be accepted as a useful agent for kidney preservation.

The effects of vasopressin in isolated rat hearts.

The roles of cGMP, prostaglandins, the entry of extracellular Ca2+ through slow channels, endothelium and V1 receptors in the negative inotropic, chronotropic and coronary vasoconstrictor responses to arginine vasopressin (AVP) have been investigated in isolated perfused rat hearts. The bolus injection of 5 x 10(-5) M AVP produced a significant decrease in contractile force, heart rate and coronary flow. AVP also significantly decreased contractile force, heart rate and coronary flow in hearts pretreated with an inhibitor of soluble guanylate cyclase methylene blue (10(-6) M), an effective drug for removing endothelium saponin (500 micrograms/ml), an inhibitor of cyclooxygenase indomethacin (10(-5) M) or a calcium channel antagonist verapamil (5 x 10(-7) M). The potent V1 receptor antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (9 x 10(-5) M) did not alter effects of AVP but the very potent V1 receptor antagonist [beta-Mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin (8 x 10(-5) M) abolished these effects. Our results suggest that AVP produces negative inotropic, chronotropic and coronary vasoconstrictor effects in isolated perfused rat hearts. cGMP, prostaglandin release and Ca2+ entry does not involve in the effects of AVP. These effects are endothelium independent and mediated by V1 receptors. The use of V1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin may be beneficial for preventing the negative inotropy, chronotropy and coronary vasoconstriction induced by AVP.

Positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of acetylcholine in isolated rat hearts: role of muscarinic receptors, prostaglandins, protein kinase C, influx of extracellular ca2+, intracellular Ca2+ release, and endothelium.

The involvement of nitric oxide (NO), muscarinic receptors, prostaglandins, calcium influx via slow calcium channels, Ca2+ release from intracellular stores, protein kinase C, and endothelium in the positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of acetylcholine (ACh) has been investigated in isolated rat hearts. The perfusion of hearts with ACh (10(-7), 5 x 10(-7), and 10(-6) M) produced marked decreases in heart rate and coronary flow and a marked increase in contractile force. Similar effects have been observed during the perfusion of hearts with ACh in the presence of Nomega-nitro-L-arginine methyl ester (L-NAME), which is an inhibitor of NO synthesis. The positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of ACh were abolished by muscarinic receptor blocker atropine. In hearts pretreated with cyclooxygenase inhibitor indomethacin, ACh significantly decreased heart rate but did not significantly affect coronary flow and contractile force. In the presence of calcium channel antagonist verapamil or protein kinase C inhibitor staurosporine, ACh produced a significant drop in heart rate but did not significantly affect coronary perfusion pressure and force of contraction. In the presence of the inhibitor of the release of Ca2+ from intracellular stores dantrolene sodium, ACh produced a significant increase in coronary perfusion pressure and a marked decline in heart rate, but did not significantly affect force of contraction. Furthermore, the disruption of endothelium by perfusing the hearts with saponin abolished the vasoconstrictor effect of ACh but did not alter negative chronotropic and positive inotropic effect. Our results suggest that ACh causes vasoconstrictor, negative chronotropic, and positive inotropic effects in isolated rat hearts. Cardiac effects of ACh are related to muscarinic receptor activation, and prostaglandins modulate ACh-induced vasoconstriction and positive inotropy. Our data also suggest that protein kinase C and calcium influx from extracellular source may be responsible for the vasoconstrictor and positive inotropic effect of ACh. The calcium release from intracellular stores may mediate the positive inotropic effect, and the vasoconstrictor effect of ACh depends on an intact endothelium.

The role of nitric oxide in the regulation of coronary flow and mechanical function of isolated, perfused rat hearts.

The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function under basal conditions and when exposed to nifedipine was studied in perfused rat hearts. Inhibition of basal release of NO by bolus injections of NG-nitro-L-arginine (L-NNA) (90 mM) and NG-nitro-L-arginine methyl ester (L-NAME) (185, 370 and 740 mM) induced significant decrease in coronary flow, contractile force and heart rate. L-NAME in the doses of 185, 370 and 740 mM also decreased significantly contractile force and heart rate during treatment with 170 microM nifedipine. However, the same doses of L-NAME caused an insignificant reduction in coronary flow in the presence of nifedipine. These findings suggest that NO has an important role in the regulation of coronary flow and mechanical performance under basal conditions and during the hearts exposed to nifedipine. Nifedipine may attenuate the myocardial ischaemia induced by the loss of NO production.

Prostaglandin-independent decrease of sheep ureter contractility induced by bradykinin.

The mechanisms that mediate the actions of bradykinin on ureteral motility are poorly defined and mediation via prostaglandins has not been examined. Therefore, the effects of bradykinin on contractility and the possible mediator role of prostaglandins have been investigated in sheep ureter. At the concentrations of 10(-8), 10(-7) and 10(-6) M, bradykinin elicited marked reductions in contractile force. When ureteral strips were treated separately with 10(-6) M indomethacin, 2 x 10(-6) M sodium salicylate and 10(-5) M aspirin, each drug produced a significant decrease in contractile force. In strips in which prostaglandin synthesis was inhibited by the above concentrations of indomethacin, sodium salicylate and aspirin, 10(-7) M bradykinin significantly decreased the contractility. From these data, we concluded that in ureter bradykinin decreases contractility via a mechanism not involving prostaglandin generation.

The effect of lanthanum on the mechanical function of the isolated perfused rat heart at different extracellular calcium concentrations.

The effects of 50 microM lanthanum (La3+) on the contractile force, rate and coronary flow of rat hearts perfused with solutions containing 2.5, 5, 7.5 mM calcium (Ca2+) have been investigated. La3+ produced a rapid and marked decrease in contractile force within 1-3 min ("early La(3+)-effect"). The inhibition of contractility by La3+ was reduced progressively when the Ca2+ ion concentration in the perfusion fluid was raised from 2.5 to 7.5 mM. However, after 10-80 min of La3+ perfusion the contractile force was increased significantly ("late La(3+)-effect"). Elevation of Ca2+ during exposure to La3+ increased its effect. During the late La(3+)-effect, a marked decrease in heart rate and a significant increase in time to reach peak tension, time for half relaxation and twitch duration was observed. High concentrations of perfusate Ca2+ decreased the chronotropic response to La3+, in contrast, elevated Ca2+ potentiated La(3+)-induced increase in time to reach peak tension, time for half relaxation and twitch duration. La3+ produced a significant decrease in coronary flow. High Ca2+ augmented the decrease coronary flow. The findings indicate that La3+ may produce marked effects on myocardial function. High extracellular Ca2+ reduces the La(3+)-induced initial decrease in force of contraction, but potentiates the late increase in contractile force by La3+. Elevated external Ca2+ also increases the effects of La3+ on twitch parameters, heart rate and coronary flow.