Oscillation frequency of skin microvascular blood flow is associated with mortality in critically ill patients

Abstract

Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism. Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases. The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined. Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion. Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05). Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05). Myocardial ATP levels were markedly improved in the sulfide-treated group. Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass. These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study. The aim of the current study was to test potential cytoprotective and anti-inflammatory effects of the novel biological mediator hydrogen sulfide in murine models. Murine J774 macrophages were grown in culture and exposed to cytotoxic concentrations of nitrosoglutathione, or peroxynitrite (a reactive species formed from the reaction of nitric oxide and superoxide). Pretreatment of the cells with sodium sulfide (60-300 µM) reduced the loss of cell viability elicited by the nitric oxide donor compound (3 mM) or by peroxynitrite (3 mM), as measured by the MTT method. Sodium sulfide did not affect cell viability in the concentration range tested. In mice subjected to bacterial lipopolysaccharide (LPS, 5 mg/kg i.p.), treatment of the animals with sodium sulfide (0.2 mg/kg/hour for 4 hours, administered in Alzet minipumps) reduced the LPSinduced increase in plasma IL-1β and TNFα levels. These responses were attenuated when animals were pretreated with the heme oxygenase inhibitor tin-protoporphyrin IX (6 mg/kg). The current results point to the cytoprotective and anti-inflammatory effects of hydrogen sulfide, in cells exposed to nitrosative stress, and in animals subjected to endotoxemia. Introduction It has been previously shown that the two forms of acute cholecystitis, acute acalculous cholecystiti...

Enhanced flow-motion complexity of skin microvascular perfusion in Sherpas and lowlanders during ascent to high altitude

“…Clinically, it has been shown that vasomotion is increased in patients with mild peripheral arterial occlusive disease (PAOD) and that those patients with enhanced vasomotion had significantly higher tissue oxygen levels than those without, despite similar blood flow 48 . Our data are also consistent with the increase in vasomotion seen in reduced perfusion states such as sepsis and cardiopulmonary bypass and in multiple organ dysfunction and mortality 49–51 . Thus, the increased strength of the association of the myogenic power band activity with LZC, is consistent with vasomotion being an important modulator of gaseous exchange under conditions of hypobaric hypoxia, when the microcirculation may tend towards a critical state.…”

Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia

“…This decreased responsiveness to endothelium dependent relaxation during a hypoxic state may be explained by an impaired vasodilatory reserve of the microvasculature in response to an ischemic stimulus (Sparks and Belloni, 1978 ; Knotzer et al, 2006 ). This phenomenon was only reported in clinical studies in patients with severe impairment of the physiological state like sepsis and multiple organ dysfunction syndrome (Haisjackl et al, 1990 ; Knotzer et al, 2006 , 2007 ; Knotzer and Hasibeder, 2007 , 2008 ). Why hypoxia and severe disease result in similar changes of microvascular reactivity is peculiar and deserves further investigations.…”

Sustained vasomotor control of skin microcirculation in Sherpas versus altitude‐naive lowlanders: Experimental evidence from Xtreme Everest 2

“…In the context of critical illness, dysregulated vasomotion is thought to participate in the development of pathophysiological states (Nilsson et al 2003). An increase in vasomotion is observed in reduced perfusion states, such as sepsis and cardiopulmonary bypass, and has been closely associated with worsening multiple organ dysfunction and mortality (Knotzer et al, 2007;Podgoreanu, Stout, El-Moalem, & Silverman, 2002;Young et al 1995). This increase in vasomotion, evident in lowlanders on exposure to altitude, might be a rescue response of the skin microvasculature to impaired oxygen utilization of the skin tissue.…”