The American journal of physiology
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Lidocaine and its permanently charged analogue QX-314 block sodium current (INa) in nerve, and by this mechanism, lidocaine produces local anesthesia. When administered clinically, lidocaine prevents cardiac arrhythmias. ⋯ Using a large suction pipette for voltage clamp and internal perfusion of single cardiac Purkinje cells, we demonstrate that a charged lidocaine analogue blocks INa not only when applied from the inside but also from the outside, unlike noncardiac tissue. This functional difference in heart predicts that a second local anesthetic binding site exists outside or near the outside of cardiac Na channels and emphasizes that the cardiac Na channel is different from that in nerve.
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Hemodynamic and metabolic variables were measured for the whole body and isolated hindlimb of anesthetized dogs during resuscitation from hemorrhagic shock, using a small volume of hypertonic saline or a larger volume of hydroxyethylstarch. Twelve dogs were bled and maintained at a mean arterial pressure (MAP) of 40 mmHg for 30 min. Six dogs were then infused with 7.5% NaCl in 5 ml/kg hydroxyethylstarch (HTS group), and six received 6% hydroxyethylstarch alone (HES group) in an amount to approximate the maximum MAP achieved with hypertonic saline. ⋯ In the isolated hindlimb, vascular resistance decreased rapidly on hypertonic saline infusion but reached similar levels at 10 min of resuscitation with both fluids. With progressive lowering of blood flow to the pump-perfused hindlimb, ability of limb muscle to extract O2 was the same for the HTS and HES groups. With hemodilution by volume replacement with acellular fluid after hemorrhage, a seemingly adequate cardiac output and arterial pressure may be underresuscitation if O2 delivery does not meet the increased O2 demand.
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To evaluate mechanisms in hemoglobinuric acute renal failure (ARF) rats were infused with hemoglobin under aciduric or alkalinuric conditions. Aciduric rats developed azotemia, distal heme casts, and proximal tubular cell (PTC) necrosis, whereas alkalinuric rats developed no renal damage. Aciduria converted hemoglobin to met-hemoglobin, which precipitated, forming distal casts and inducing ARF. ⋯ Iron chelation (deferoxamine)/hydroxyl radical scavenger (Na benzoate) therapy did not mitigate this exacerbation of ischemic injury, suggesting a nonoxidant mechanism. We conclude that H is nephrotoxic, particularly when intratubular obstruction facilitates PTC heme uptake. Thus aciduria-induced met-hemoglobin cast formation and concomitant ischemic renal injury predispose to its nephrotoxic effect.
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The cardiovascular effects of althesin (ALT) and urethan-chloralose (UC) anesthesia were compared in conscious, chronically instrumented rats. Althesin had no effect on arterial pressure or base-line resistance in the renal, superior mesenteric, and hindquarters vasculatures but increased heart rate. In contrast, UC decreased arterial pressure, heart rate, and mesenteric resistance. ⋯ Similarly, UC but not ALT induced vasopressin-dependent vascular tone. Ganglionic blockade indicated that peripheral neurogenic tone was not altered by ALT anesthesia. These data suggest that althesin produces fewer hemodynamic disturbances than urethan-chloralose and largely maintains cardiovascular regulation intact.
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Metabolic acidosis inhibits and alkalosis enhances ketoacid production in ketotic humans and animals. To compare these effects with those of superimposed respiratory acid-base disturbances, ketone output was evaluated in awake ketotic rats during metabolic (intravenous infusions of HCl or NaHCO3) or respiratory (hyper or hypocapnia) disorders. With decreases in blood pH of 0.1-0.2 units over 3 h, blood ketone concentrations significantly decreased an average of 1.9 mM (metabolic) and 1.1 mM (respiratory) and urinary ketone excretion rates significantly decreased by 1.3 mumol/min (metabolic). ⋯ Changes in blood pH correlated with changes in urinary ketone excretion rates in both metabolic (r = 0.87) and respiratory (r = 0.67) acid-base disturbances. The alterations occurred promptly and were rapidly reversible. These findings indicate that modest changes in systemic pH from metabolic or respiratory acid-base disturbances modify net ketoacid production in ketotic rats, confirm pH control of endogenous acid output as an acid-base regulator, and show that systemic pH, not bicarbonate concentration, mediates the process.