Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction

Kemp, Rafael; Castro‐e‐Silva, Orlando; Santos, José Sebastião dos; Sankarankutty, Ajith Kumar; Correa, Rodrigo Borges; Baldo, Caroline Floreoto; Souza, Maria Elisa; Jordani, Maria Cecília

doi:10.1590/s0102-86502008000700012

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…The lower Ca 2+ threshold for triggering mPTP opening in bupivacaine group was not due to the lower quality of the mitochondrial preparation in this group, as the respiratory control ratio in both Bup and LE groups was greater than 4 (Fig. 3A–C)(35;36). Our results highlight the role of mPTP in reversal of cardiotoxicity by LE.…”

Section: Discussionmentioning

confidence: 82%

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats*

Partownavid

Umar

et al. 2012

Critical Care Medicine

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OBJECTIVES Lipid Emulsion (LE) has been shown to be effective in resuscitating bupivacaine-induced cardiac arrest but its mechanism of action is not clear. Here we investigated whether fatty acid oxidation is required for rescue of bupivacaine induced cardiotoxicity by LE in rats. We also compared the mitochondrial function and calcium threshold for triggering of mitochondrial permeability transition pore (mPTP) opening in bupivacaine-induced cardiac arrest before and after resuscitation with LE. DESIGN Prospective, randomized, animal study. SETTING University Research Laboratory. SUBJECTS Adult male Sprague-Dawley rats. INTERVENTIONS Asystole was achieved with a single dose of bupivacaine (10mg/kg over 20seconds, i.v.) and 20% LE infusion (5ml/kg bolus, and 0.5ml/kg/min maintenance) with cardiac massage started immediately. The rats in CVT group were pretreated with a single dose of fatty acid oxidation inhibitor CVT (0.5, 0.25, 0.125 or 0.0625mg/kg bolus i.v.) 5min prior to inducing asystole by bupivacaine overdose. Heart rate (HR), ejection fraction (EF), fractional shortening (FS), the threshold for opening of mPTP, oxygen consumption and membrane potential were measured. The values are Mean±SEM. MEASUREMENTS AND MAIN RESULTS Administration of bupivacaine resulted in asystole. ILP infusion improved the cardiac function gradually as the EF was fully recovered within 5min (EF=64±4% and FS=36±3%, n=6) and heart rate increased to 239±9 beats/min (71% recovery, n=6) within 10min. LE was only able to rescue rats pretreated with low dose of CVT (0.0625mg/kg) (HR=~181±11 beats/min at 10 min, recovery of 56%; EF=50±1%; FS=26±0.6% at 5min, n=3) but was unable to resuscitate rats pretreated with higher doses of CVT (0.5, 0.25 or 0.125mg/kg). The calcium retention capacity in response to Ca2+ overload was significantly higher in cardiac mitochondria isolated from rats resuscitated with 20% LE compared to the group that did not receive ILP after bupivacaine-overdose (330±42 vs. 180±8.2 nmol/mg-mitochondrial protein, p<0.05, n=3 in each group). The mitochondrial oxidative rate and membrane potential were similar in bupivacaine group before and after resuscitation with LE infusion. CONCLUSIONS Fatty acid oxidation is required for successful rescue of bupivacaine induced cardiotoxicity by LE. This rescue action is associated with inhibition of mitochondrial permeability transition pore opening.

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Section: Discussionmentioning

confidence: 82%

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats*

Partownavid

Umar

et al. 2012

Critical Care Medicine

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“…The importance of ATP as a functional sympathetic neurotransmitter in blood vessels depends on the species, the vascular bed, the type of blood vessel and the pathology analysed 59 . In this sense, changes in purinergic cardiovascular signalling have been described in liver pathologies 60 61 . We have observed a substantial phentolamine-resistant contractile response, greater in mesenteric segments from LC rats, which was abolished after adding the P2-purinoceptor antagonist suramin.…”

Section: Discussionmentioning

confidence: 99%

Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations

Sastre

Caracuel

Prieto

et al. 2016

Sci Rep

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We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis.

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“…Kemp et al ., showed that cellular respiration of the “jaundiced heart” is depressed. This depression was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, suggesting a role for latent cardiac impairment in development of haemodynamic decompensation in cholestasis . The precise mechanism(s) of cholestasis‐induced cardiac complications are not completely understood.…”

Section: Cardiac Abnormalities In Cholestasismentioning

confidence: 99%

Cardiovascular abnormalities in obstructive cholestasis: the possible mechanisms

Moezi

Dehpour

2012

Liver International

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Cholestatic liver disease is associated with widespread derangements in the cardiovascular system, such as bradycardia, hypotension, QT prolongation and peripheral vasodilation; it is also associated with increased susceptibility to postoperative renal failure and haemorrhagic shock. A number of cellular signalling pathways have been shown to contribute to these abnormalities. In this article, we briefly review recent in vivo and in vitro findings in the field in an attempt to highlight the areas of agreement and areas of controversy. In this review, we will summarize pathogenic mechanisms underlying cardiac and vascular abnormalities in obstructive cholestasis. It seems that cardiovascular dysfunction is likely because of bile acids as one of the predominant factors. Other important factors which might play roles in these abnormalities are increased nitric oxide, endogenous opioids and endocannabinoids. These three factors interact with each other to exert vasodilation and impaired cardiovascular responses to sympathetic stimulation.For many years, surgeons were puzzled and distressed by the frequent complications of hypotension and kidney failure after surgery on patients with obstructive jaundice (1-3). Increased recognition and awareness of this clinical problem have led to extensive clinical and laboratory investigations, resulting in a better appreciation of the relationship between the liver, the kidney and the cardiovascular system. The first to make a systematic study of the bradycardia of jaundice was RÖ hrig, in 1863, who showed that the bile salts are responsible for the bradycardia and low blood pressure of jaundice (4). In 1911, Clairmont and von Haberer first described the occurrence of renal failure developing after surgery for obstructive jaundice. Following these original observations, numerous clinical series have been reported in the literature, all of which point to a strong association between post-surgical renal failure and obstructive jaundice. A review of the different series indicates that the overall mortality rate for patients undergoing surgery for obstructive jaundice is 16% to 18%. Acute renal failure occurs in approximately 8% to 10% of patients requiring surgery for relief of obstructive jaundice and contributes to eventual mortality in 70% to 80% of those who develop it (5).In this review, we attempt to summarize the pathogenic mechanisms underlying cardiac and vascular abnormalities in cholestasis. Human data in this field is relatively scarce; majority of the findings discussed in this article are based on animal studies. The Figure 1 summarizes the major pathologic mechanisms in the blood vessels and/or the heart. Cardiac abnormalities in cholestasisThe association of obstructive jaundice with bradycardia has been known for over a century (5). It is also well known that cholestatic liver disease is associated with hypotension (6, 7), QT prolongation (8) and hyporesponsiveness of the heart to adrenergic stimulation (9, 10). Literature reports also have described a card...

show abstract

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction

Cited by 6 publications

References 16 publications

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats*

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats*

Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations

Cardiovascular abnormalities in obstructive cholestasis: the possible mechanisms

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