Myocardial dysfunction and potential cardiac hypoxia in rats induced by carbon monoxide inhalation.
ABSTRACT Results from both animal and human being studies provide evidence that inhalation of concentrations of carbon monoxide (CO) at around 100 ppm has antiinflammatory effects. These low levels of CO are incriminated in ischemic heart diseases experienced by cigarette smokers and, in some cases, from air pollution. Although neurologic mechanisms have been investigated, the effects of CO on cardiovascular function are still poorly understood.
The effects of CO (250 ppm; 90 min) inhalation on myocardial function were investigated in isolated heart of rats killed immediately, and 3, 24, 48, and 96 h after CO exposure. CO exposure at 250 ppm resulted in an arterial carboxyhemoglobin (HbCO) level of approximately 11%, which was not associated with changes in mean arterial pressure and heart rate. CO exposure induced coronary perfusion pressure increases, which were associated with endothelium-dependent and -independent vascular relaxation abnormalities. CO-induced coronary vascular relaxation perturbations were observed in the presence of increased heart contractility. Spontaneous peak to maximal Ca(2+)-activated left ventricular pressure ratio was markedly increased in CO-exposed rats, indicating increases in myofilament calcium sensitivity. Heart cyclic guanosine monophosphate/cAMP ratio and myocardial permeabilized fiber respiration (complex intravenous activity) were reduced in CO-exposed rats, which lasted after 48 h of reoxygenation in air.
These findings suggest that CO deteriorates heart oxygen supply to utilization and potentially may induce myocardial hypoxia through mechanisms that include increased oxygen demand due to increased contractility, reduced coronary blood flow reserve, and cardiomyocyte respiration inhibition.
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ABSTRACT: Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.Journal of cardiovascular pharmacology 06/2012; 60(3):299-309. · 2.83 Impact Factor
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ABSTRACT: Carbon monoxide pollution frequently occurs due to auto exhaust, industrial emissions, and/or cigarette smoke. Exogenous and endogenous carbon monoxide affects blood pressure; however, the relation of carbon monoxide exposure to pregnancy hypertension has not been systematically examined. For the present study the authors recruited a total of 2,707 apparently healthy, non-obese, non-smoking mothers, aged between 15 and 40 years, who had singleton births, and who lived within two miles of the selected air monitoring stations in Tehran, Iran, to study the relation of ambient carbon monoxide to pregnancy hypertension (>140 mmHg systolic and/or >90 mmHg diastolic after the 20th week of gestation). A relatively small but statistically significant elevation in mean postpartum diastolic blood pressure (mean ± SD, 69.5 ± 9.8 mmHg) was observed in the mothers' who were exposed to relatively high ambient carbon monoxide (mean = 14.1 ppm) compared to mothers exposed to lower carbon monoxide (mean = 1.8 ppm) concentrations (mean ± SD, 68.0 ± 8.3 mmHg, p < 0.01). The authors found twice the rate of pregnancy hypertension in the relatively higher carbon monoxide exposed mothers than the mothers with lower exposure (adjusted odds ratio = 2.02, 95% CI 1.35-3.03). Findings of the present study suggest that high level ambient carbon monoxide exposure is associated with pregnancy hypertension.Women & Health 11/2011; 51(8):724-38. · 1.00 Impact Factor