Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45 minutes global ischemia and 60 minutes reperfusion. Coronary flow, isovolumetric left ventricular pressure and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.

Previously, we demonstrated that very low-frequency (VLF) blood pressure variability (BPV) depends on voltage-gated L-type Ca(2+)-channels, suggesting that autoregulation of blood flow and/or myogenic vascular function significantly contributes to VLF BPV. To further substantiate this possibility, we tested the hypothesis that the frequency response characteristic of whole body autoregulation of blood flow is consistent with the frequency range of VLF BPV (0.02-0.2 Hz) in rats. In anesthetized rats (n = 11), BPV (0.016-0.5 Hz) was induced by computer-regulated cardiac pacing while blood pressure, heart rate, and cardiac output (CO) were recorded during control conditions (NaCl, 1 ml/h iv) and during alpha(1)-adrenergic receptor stimulation (phenylephrine, 1 mg.ml(-1).h(-1) iv) that has been reported to facilitate myogenic vascular function. Baroreceptor-heart rate reflex responses were elicited to confirm a functional baroreflex despite anesthesia. During control conditions, transfer function analyses between mean arterial pressure (MAP) and CO, and between MAP and total vascular conductance (CO/MAP) indicated autoregulation of blood flow at 0.016 Hz, passive vascular responses between 0.033 and 0.2 Hz, and vascular responses compatible with baroreflex-mediated mechanisms at 0.333 and 0.5 Hz. Stimulation of alpha(1)-adrenergic receptors extended the frequency range of autoregulation of blood flow to frequencies up to 0.033 Hz. In conclusion, depending on sympathetic vascular tone, whole body autoregulation of blood flow operates most effectively at frequencies below 0.05 Hz. This frequency range overlaps with the lower end of the frequency band of VLF BPV in rats. Baroreceptor reflex-like mechanisms contribute to LF (0.2-0.6 Hz) but not VLF BPV-induced vascular responses.

Previous studies from our laboratory suggested that myogenic vascular function contributes to VLF BPV. Here we tested the hypothesis that the dynamic properties of whole body autoregulation of blood flow is consistent with the frequency range of VLF BPV (0.02‐0.2 Hz) in rats.In anesthetized rats (n=11) BPV (0.016‐0.5 Hz) was induced by computer‐regulated cardiac pacing while blood pressure and cardiac output (CO) were recorded during control conditions (NaCl, 1mL/h i.v.) and α1‐adrenergic receptor stimulation (phenylephrine, 1mg/mL/h i.v.) that has been reported to facilitate myogenic vascular function.During control conditions, transfer function analyses between mean arterial pressure (MAP) and CO and between MAP and total vascular conductance (CO/MAP) indicated autoregulation of blood flow at 0.016 Hz, passive vascular responses between 0.033 Hz and 0.2 Hz, and baroreflex‐like responses at 0.333 Hz and 0.5 Hz. Stimulation of α1‐adrenergic receptors extended the frequency range of autoregulation of blood flow to frequencies up to 0.033 Hz.Depending on sympathetic vascular tone, whole body autoregulation of blood flow most effectively operates at frequencies below 0.05 Hz. This frequency range is consistent with VLF BPV in rats. Baroreceptor reflex‐like mechanisms contribute to LF (0.2‐0.6 Hz) but not VLF BPV‐induced vascular responses.Supported by the American Heart Association (0630329N)