Obesity plays a pivotal role in metabolic and cardiovascular diseases. Certain types of obesity may be related to alcohol ingestion, which itself leads to impaired cardiac function. This study analyzed basal and ethanol-induced cardiac contractile response using left-ventricular papillary muscles and myocytes from lean and obese Zucker rats. Contractile properties analyzed include: peak tension development (PTD), peak shortening amplitude (PS), time to PTD/PS (TPT/TPS), time to 90% relaxation/relengthening (RT₉₀/TR₉₀) and maximal velocities of contraction/shortening and relaxation/relengthening (±VT and ±dL/dt). Intracellular Ca²⁺ transients were measured as fura-2 fluorescence intensity (ΔFFI) changes and fluorescence decay time (FDT). In papillary muscles from obese rats, the baseline TPT and RT₉₀ were significantly prolonged accompanied with low to normal PTD and ±VT compared to those in lean rats. Muscles from obese hearts also exhibited reduced responsiveness to postrest potentiation, increase in extracellular Ca²⁺ concentration, and norepinephrine. By contrast, in isolated myocytes, obesity reduced PS associated with a significant prolonged TR₉₀, normal TPS and ±dL/dt. Intracellular Ca²⁺ recording revealed decreased resting Ca²⁺ levels and prolonged FDT. Acute ethanol exposure (80–640 mg/dl) caused comparable concentration-dependent inhibitions of PTD/PS and ΔFFI, associated with reduced ±VT in both groups. Collectively, these results suggest altered cardiac contractile function and unchanged ethanol-induced depression in obesity.

We studied the effect of ovariectomy (OVX) on cardiac contraction in myocytes maintained under a ‘diabetes-simulated high-glucose’ environment. Female rats were ovariectomized or sham operated (SHAM) and kept for 6 weeks. Isolated myocytes were maintained in a diabetes-simulated high [glucose] medium (HG; 25.5 mM) for 24 h before mechanical properties were measured. Contractile indices analyzed included peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR₉₀), maximal velocity of shortening and relengthening (± dL/dt), intracellular Ca²⁺ fura-2 fluorescence intensity and decay rate (τ). Nitric oxide synthase (NOS) activity was also evaluated. OVX myocytes displayed a longer TR₉₀, slower ± dL/dt, lower fluorescence intensity and higher τ (slower decay rate) when compared to SHAM myocytes. In the SHAM group, HG exerted diabetes-like contractile dysfunctions, including depressed PS, prolonged TR₉₀, reduced fluorescence intensity, higher τ and enhanced NOS activity when compared to myocytes maintained in low [glucose] medium (5.5 mM). Interestingly, the HG- induced mechanical alterations were significantly exaggerated (TPS, TR₉₀ and τ), reversed (PS and NOS) or lost (± dL/dt and fluorescence intensity) in the OVX group. These data suggest that ovarian hormones play a role in the regulation of cardiac contractile function, and may have potentially protective effects against diabetes-associated cardiac dysfunction.