Cardiovascular hyporesponsiveness to norepinephrine, propranolol and nitroglycerin in portal-hypertensive and aged rats

Polio, John; Sieber, Cornel; Lerne, Emanuel; Groszmann, Roberto J.

doi:10.1002/hep.1840180120

Cited by 8 publications

(9 citation statements)

References 39 publications

(48 reference statements)

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“…13,15 The responses in MAP to both vasopressin analogues were similar in PVL and SHAM rats. These findings are remarkable, because cardiovascular hyporesponsiveness to vasoconstrictors is a well-known feature of portal hypertension, [23][24][25][26][27][28][29][30] and has also been observed in the present study as systemic and mesenteric hyporesponsiveness to phenylephrine. The mesenteric arterial hyperresponsiveness of PVL rats to vasopressin analogues, as described here in vivo, is unlikely to be the result of increased vasopressin receptor density or affinity, because it is not observed in isolated perfused mesenteric arterial beds of portal hypertensive rats.…”

Section: Discussionsupporting

confidence: 79%

Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats

et al. 1998

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We recently reported that vasopressin analogues correct the in vitro vascular hyporeactivity to adrenergic vasoconstrictors in portal hypertensive rats. The aim of the present study was to determine whether vasopressin reduces splanchnic blood flow in portal vein-ligated (PVL) rats by restoring vasoconstrictor responsiveness in vivo. The ultrasonic transit time-shift technique was used for blood flow measurements. At basal conditions, blood flow through the superior mesenteric artery was elevated 1.6-fold in PVL rats as compared with sham-operated (SHAM) control rats. PVL rats also exhibited blunted mesenteric constrictor responses to the adrenoceptor agonist, phenylephrine (0.03-1 mol · min ؊1 · kg ؊1 ). Terlipressin (2-20 g · kg ؊1 ) and arginine vasopressin (3-300 pmol · min ؊1 · kg ؊1 ) dosedependently reduced, and at the highest doses, even abolished, the difference in mesenteric blood flow (MBF) between PVL and SHAM rats. When expressed as percent changes relative to baseline, mesenteric arterial responses to terlipressin and arginine vasopressin were found to be enhanced in PVL rats as compared with SHAM rats. Moreover, pretreatment with terlipressin (20 g · kg ؊1 ) reversed the mesenteric hyporesponsiveness to phenylephrine of PVL rats. These vasopressin effects were independent of the nitric oxide (NO) pathway, because they were not mimicked by inhibition of NO synthesis with N G -nitro-Larginine methyl ester (L-NAME) (0.1-10 mg · kg ؊1 ). These data indicate that pharmacological doses of vasopressin reverse the splanchnic hyperemia by restoring the responsiveness to adrenergic vasoconstrictors in portal hypertensive rats. (HEPATOLOGY 1998;28:646-654.)Portal hypertension is associated with hyperdynamic circulation, which is characterized by decreased peripheral resistance and increased cardiac output. Although vasodilation is present in most vascular beds, it is especially important in the splanchnic circulation. Blood flow to the abdominal organs in portal hypertension is about twice as high as under normal conditions, 1,2 a fact that has been shown to be responsible for the maintenance of chronically elevated portal pressure. 2,3 Several possible explanations for the splanchnic vasodilation have been raised, including circulating vasodilators, decreased reactivity of the splanchnic arteries to endogenous vasoconstrictors, and/or local overproduction of vasodilator mediators such as nitric oxide (NO), of which evidence for its involvement has increasingly accumulated. 4,5 Vasopressin analogues are currently used in the treatment of acute variceal bleeding in cirrhotic patients, because they effectively reduce splanchnic blood flow, and thus portal pressure as well. [6][7][8] In addition, ornipressin has been shown to normalize systemic and renal hemodynamics and renal function in decompensated cirrhosis. 9 We recently provided data that vasopressin analogues reverse the vascular hyporeactivity to adrenoceptor stimulation in isolated perfused mesenteric arterial beds of portal hypertensive rats. 10,11 T...

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Section: Discussionsupporting

confidence: 79%

Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats

et al. 1998

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“…However, in an experimental study [43], vasopressin proved to be inferior to norepinephrine in terms of improving hepatosplanchnic blood flow. The response to both norepinephrine and vasopressin is blunted in patients with cirrhosis [44, 45]. …”

Section: Resultsmentioning

confidence: 99%

Anesthetic Considerations in Hepatectomies under Hepatic Vascular Control

et al. 2012

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Background. Hazards of liver surgery have been attenuated by the evolution in methods of hepatic vascular control and the anesthetic management. In this paper, the anesthetic considerations during hepatic vascular occlusion techniques were reviewed. Methods. A Medline literature search using the terms “anesthetic,” “anesthesia,” “liver,” “hepatectomy,” “inflow,” “outflow occlusion,” “Pringle,” “hemodynamic,” “air embolism,” “blood loss,” “transfusion,” “ischemia-reperfusion,” “preconditioning,” was performed. Results. Task-orientated anesthetic management, according to the performed method of hepatic vascular occlusion, ameliorates the surgical outcome and improves the morbidity and mortality rates, following liver surgery. Conclusions. Hepatic vascular occlusion techniques share common anesthetic considerations in terms of preoperative assessment, monitoring, induction, and maintenance of anesthesia. On the other hand, the hemodynamic management, the prevention of vascular air embolism, blood transfusion, and liver injury are plausible when the anesthetic plan is scheduled according to the method of hepatic vascular occlusion performed.

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“…From the mid-1980s to the early 1990s, several investigators showed that cardiac contractile reserve is diminished in different rat models of nonalcoholic cirrhosis [16][17][18][19]. Notable is the landmark study of Caramelo and colleagues [17], who infused saline into rats with carbon tetrachlorideinduced cirrhosis.…”

Section: Systolic Dysfunctionmentioning

confidence: 99%

Cirrhotic cardiomyopathy

2008

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Cirrhotic cardiomyopathy is a recently recognized condition in cirrhosis consisting of systolic incompetence under condition of stress, diastolic dysfunction related to altered diastolic relaxation, and electrophysiological abnormalities in the absence of any known cardiac disease. It can be diagnosed by using a combination of electrocardiograph, 2-dimensional echocardiography, and various serum markers such as brain natriuretic factor. The underlying pathogenetic mechanisms include abnormalities in the b-adrenergic signaling pathway, altered cardiomyocyte membrane fluidity, increased myocardial fibrosis, cardiomyocyte hypertrophy, and ion channel defects. Various compounds for which levels are elevated in cirrhosis such as nitric oxide and carbon monoxide can also exert a negative inotropic effect on the myocardium, whereas excess sodium and volume retention can lead to myocardial hypertrophy. Various toxins can also aggravate the ion channel defects, thereby widening the QRS complex causing prolonged QT intervals. Clinically, systolic incompetence is most evident when cirrhotic patients are placed under stress, whether physical or pharmacological, or when the extent of peripheral arterial vasodilatation demands an increased cardiac output as in the case of bacterial infections. Acute volume overload such as immediately after insertion of a transjugular intrahepatic portosystemic shunt or after liver transplantation can also tip these cirrhotic patients into cardiac failure. Treatment of cirrhotic cardiomyopathy is unsatisfactory. There is some evidence that b-blockade may help some cirrhotic patients with baseline prolonged QT interval. Long-term aldosterone antagonism may help reduce myocardial hypertrophy. Future studies should include further elucidation of pathogenetic mechanisms so as to develop effective treatment strategies.

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Cardiovascular hyporesponsiveness to norepinephrine, propranolol and nitroglycerin in portal-hypertensive and aged rats

Cited by 8 publications

References 39 publications

Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats

Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats

Anesthetic Considerations in Hepatectomies under Hepatic Vascular Control

Cirrhotic cardiomyopathy

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