American journal of physiology. Heart and circulatory physiology
-
Am. J. Physiol. Heart Circ. Physiol. · Sep 2009
Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic skin in mice.
Local hypoxia, as due to trauma, surgery, or arterial occlusive disease, may severely jeopardize the survival of the affected tissue and its wound-healing capacity. Initially developed to replace blood transfusions, artificial oxygen carriers have emerged as oxygen therapeutics in such conditions. The aim of this study was to target primary wound healing and survival in critically ischemic skin by the systemic application of left-shifted liposomal hemoglobin vesicles (HbVs). ⋯ Six days postoperatively, flap tissue survival was increased from 33% (control) to 57% (P < 0.01) and primary healing of the ischemic wound margins from 6.6 to 12.7 mm (P < 0.05) after HbV injection. In addition, higher capillary counts and endothelial nitric oxide synthase expression (both P < 0.01) were found in the immunostained flap tissue. We conclude that left-shifted HbVs may ameliorate the survival and primary wound healing in critically ischemic skin, possibly mediated by endothelial nitric oxide synthase-induced neovascularization.
-
Am. J. Physiol. Heart Circ. Physiol. · Aug 2009
Decreased upright cerebral blood flow and cerebral autoregulation in normocapnic postural tachycardia syndrome.
Postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance, has signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits consistent with reductions in cerebrovascular perfusion. We hypothesized that young, normocapnic POTS patients exhibit abnormal cerebral autoregulation (CA) that results in decreased static and dynamic cerebral blood flow (CBF) autoregulation. All subjects had continuous recordings of mean arterial pressure (MAP) and CBF velocity (CBFV) using transcranial Doppler sonography in both the supine supine position and during a 70 degrees head-up tilt. ⋯ Static CA may be less effective in POTS patients compared with controls, since immediately after tilt CBFV decreased more in POTS patients and was highly oscillatory and autoregulation did not restore CBFV to baseline values until the subjects became supine. Dynamic CA may be less effective in POTS patients because MAP and CBFV during tilt became almost perfectly synchronous. We conclude that dynamic and static autoregulation of CBF are less effective in POTS patients compared with control subjects during orthostatic challenge.
-
Am. J. Physiol. Heart Circ. Physiol. · Aug 2009
Induced overexpression of Na+/Ca2+ exchanger transgene: altered myocyte contractility, [Ca2+]i transients, SR Ca2+ contents, and action potential duration.
We have produced mice in which expression of the rat cardiac Na(+)/Ca(2+) exchanger (NCX1) transgene was switched on when doxycycline was removed from the feed at 5 wk. At 8 to 10 wk, NCX1 expression in induced (Ind) mouse hearts was 2.5-fold higher but protein levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase, alpha(1)- and alpha(2)-subunits of Na(+)-K(+)-ATPase, phospholamban, ryanodine receptor, calsequestrin, and unphosphorylated and phosphorylated phospholemman were unchanged compared with wild-type (WT) or noninduced (non-Ind) hearts. There was no cellular hypertrophy since WT, non-Ind, and Ind myocytes had similar whole cell membrane capacitance. ⋯ In vivo close-chest catheterization demonstrated similar contractility and relaxation among the three groups of mice, both at baseline and after stimulation with isoproterenol. We conclude that induced expression of NCX1 transgene resulted in altered [Ca(2+)](i) homeostasis, myocyte contractility, and action potential morphology. In addition, heart failure did not occur 3 to 5 wk after NCX1 transgene was induced to be expressed at levels found in diseased hearts.
-
Am. J. Physiol. Heart Circ. Physiol. · Aug 2009
sGC(alpha)1(beta)1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models.
Altered cGMP signaling has been implicated in myocardial depression, morbidity, and mortality associated with sepsis. Previous studies, using inhibitors of soluble guanylate cyclase (sGC), suggested that cGMP generated by sGC contributed to the cardiac dysfunction and mortality associated with sepsis. We used sGC(alpha)(1)-deficient (sGC(alpha)(1)(-/-)) mice to unequivocally determine the role of sGC(alpha)(1)beta(1) in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin- and TNF-induced shock. ⋯ Similarly, Ca(2+) handling and cell shortening were impaired to a greater extent in cardiomyocytes isolated from sGC(alpha)(1)(-/-B6) than WT mice after endotoxin challenge. Importantly, morbidity and mortality associated with inflammatory shock induced by endotoxin or TNF were increased in sGC(alpha)(1)(-/-B6) compared with WT mice. Together, these findings suggest that cGMP generated by sGC(alpha)(1)beta(1) protects against cardiac dysfunction and mortality in murine inflammatory shock models.
-
Am. J. Physiol. Heart Circ. Physiol. · Jul 2009
The effects of propofol on vascular function in mesenteric arteries of the aging rat.
Hypotension following administration of propofol, an anesthetic agent, is strongly predicted by advanced age and is partly due to direct vasodilation. We hypothesized that propofol increases nitric oxide (NO)-mediated vasodilation by enhancing its bioavailability in the aged adult vasculature, leading to greater vasodilation than in the young adult. Small mesenteric arteries from rats aged 13-15 versus 3 to 4 mo were compared in this study. ⋯ Pretreatment with SOD and catalase increased relaxation to ACh in aged arteries similar to propofol. In conclusion, propofol causes relaxation in small mesenteric arteries in an endothelial-dependent and independent manner and increases ACh-induced relaxation in aged arteries. Interestingly, propofol inhibits EDHF-mediated relaxation but increases availability of NO, which leads to overall vascular relaxation.