Differential effects of acute ethanol treatment on cardiac contractile function in young adult and senescent mice.

It is understood that marked biochemical, molecular, and performance alterations occur in cardiovascular tissues related to aging. It is logical, therefore, that differences in the cardiovascular response to ethanol consumption, when comparing younger with older individuals, may exist. We compared the left ventricular function of 6- and 15-month-old (senescent) mice and 16-month-old (senescent) inducible nitric oxide synthase knockout mice (n=7 each) before and subsequent to acute treatment with 60% ethanol (2 g/kg, i.p.). A Millar 1.4 Fr conductance/micromanometer catheter was placed into the left ventricle of the mice for acquisition of pressure-volume loops. Heart contractile functions were significantly decreased in the senescent group, compared with findings in the younger mice. Subsequent to ethanol treatment, the younger mice showed a significant reduction in cardiac function, with a 28% decrease in cardiac index, a 29% decrease in end-systolic elastance, and a 16% decrease in preload recruitable stroke work (P<.01). Conversely, the senescent mice showed significantly increased contractile function, with a 40% increase in end-systolic elastance (P<.01) and a 19% increase in preload recruitable stroke work (P<.05). The myocardial cyclic guanosine monophosphate levels were significantly higher in the older group (P<.002), and subsequent to ethanol treatment, they were decreased by 68.5% (P<.001). Northern blot analysis demonstrated inducible nitric oxide synthase message only in senescent myocardial tissues. Moreover, the cardiac function of senescent inducible nitric oxide synthase knockout mice was comparable with that of young mice, and after ethanol treatment, cardiac function decreased significantly, just as that for young mice did, with a 26% decrease in cardiac index (P<.05) and a 23% decrease in preload recruitable stroke work (P<.01). It was concluded that the differential cardiovascular function and response to acute ethanol

Validation of conductance catheter system for quantification of murine pressure-volume loops.

The purpose of this study was to define the validation methods and outcomes of a conductance catheter system specifically for in vivo murine cardiac hemodynamic analysis. To express the relationship between conductance and blood volumes, we used an in vitro model to derive a volume-conductance line. The volume-conductance line was used to compute raw volume from the modified conductance signals. The parallel volume was calibrated with hypertonic (15%) saline injected from extrajugular vein. The ventricular volume was computed by raw volume minus parallel volume. The accuracy of conductance volumetric measurements was validated with a static in situ infusion of calibrated volumes of whole blood injected into arrested left ventricles. In vivo dynamic measurements were performed with 24 C57B1/6 mice, 6 months old; for comparison of established values. The in situ model showed that after calibration, the experimental coefficient, alpha, was equal to 1 and the measured volume by conductance catheter was equal to the true volume of the left ventricle (y = 0.982x + 0.513, p < .0001). For the in vivo models, the end-diastolic volumes and the stroke volumes and cardiac output determined with the conductance catheter system were 17.3 +/- 1.0 microL, 10.6 +/- 0.9 microL, and 6.0 +/- 0.5 mL/min, respectively. We validated the relationship between measured volume by conductance catheter and the true volume and demonstrated the accuracy of the volume-conductance line for conversion of conductance to volume.

Cocaine injection and coxsackievirus B3 infection increase heart disease during murine AIDS.

Coxsackievirus initiates myocarditis especially in the immunologically deficient or immature. To test whether Coxsackievirus B3 (CVB3) induced pronounced cardiomyopathy during severe immune dysfunction of murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3. Some were also injected daily with cocaine hydrochloride in 0.9% saline solution (30 mg/kg) intraperitoneally, because cocaine also suppresses cellular immune response. Heart tissue was analyzed histopathologically. Mice experiencing concurrent retrovirus and Coxsackievirus infection had a high degree of cardiac lesions consistent with myopathy compared with findings in uninfected animals (p <.05). Cocaine injection during murine retrovirus infection greatly exacerbated the pathogenesis of Coxsackievirus infection. C57BL/6 mice, essentially resistant to Coxsackievirus-induced cardiomyopathy, became susceptible during the immune dysfunction in murine AIDS. This suggests that retrovirus infection causes conditions favoring Coxsackie-induced cardiac lesions. Interleukin (IL)-2 and IL-4 expression by splenocytes from the dually infected retrovirus and Coxsackievirus group showed no significant differences when the animals were also cocaine treated. However tumor necrosis factor TNF-alpha production was significantly decreased in dually infected retrovirus + Coxsackievirus mice treated with cocaine, compared with findings in various controls (p <.05).