Ori S. Better

Factors affecting sperm motility. vii. sperm viability as affected by change of ph and osmolarity of semen and urine specimens

The effects of pH and osmolarity of semen and urine specimens on motility and velocity of human spermatozoa were studied objectively with the aid of the multiple exposure photography (MEP) method. The pH of fresh ejaculates ranged from 7.2 to 8.2 and specimens were slightly hyperosmotic ranging between 300 to 380 mOsm/kg. Gradually changing the pH and osmolarity to either side of normal values led to progressive loss of sperm motility. However, sperm velocity was slightly increased by mild alkalinization and hyperosmolarity. Spermatozoa that became immobilized by acidification regained their motility shortly after pH was restored to normal values. In the majority of instances spermatozoa lost their motility when mixed with fresh urine specimens. Neutralization of urinary pH could not protect them from this effect unless urine osmolarity was also isotonically adjusted. It is suggested that patients with retrograde ejaculation should adequately increase their fluid intake before recovery of sperm from their bladder for artificial insemination.

Jaundice, the Circulation and the Kidney

(Fig. 1) Cholemia per se (i.e. independent of parenchymal liver damage) causes a profound disturbance of systemic hemodynamics. This includes decrease in total peripheral vascular resistance, and possible impairment of left ventricular performance. These, in turn, lead to a decrease in effective blood volume, a tendency to hemorrhagic shock and prerenal failure. Early in the course of cholemia , the natriuretic effects of bile salts in the circulation may aggravate the hypovolemia. In marked contrast to the decrease in total peripheral vascular resistance, the regional vascular beds of the kidney and the brain constrict during cholemia . The combined effect of cholemia may thus lead to redistribution of cardiac output away from the kidney and the brain. When parenchymal liver damage complicates obstructive jaundice, the tendency to arterial hypotension is aggravated. The overall interrelationship between jaundice and circulatory homeostasis is depicted in figure 1.

Management of Shock and Acute Renal Failure in Casualties Suffering from the Crush Syndrome

Widespread muscle crush injury is often associated with profound hemodynamic shock and myoglobinuric acute renal failure (ARF). The main reason for the shock is rapid uptake by the injured muscles of a substantial portion of extracellular fluid. The shock is aggravated by NO-dependent vasodilation in the injured muscles and by hyperkalemia and hypocalcemia, which suppress the entire cardiovascular tree. Treatment consists of early massive volume replacement and forced alkaline solute (mannitol) diuresis. With this regimen it is possible to increase survival of life and limbs, and prevent myoglobinuric ARF. Our preliminary experience suggests that i.v. hypertonic mannitol is protective also to the injured muscle and can be used as a noninvasive adjunct in the management of compartment syndrome in man. Moreover, by preserving muscular integrity, mannitol can conceivable reduce leakage of the nephrotoxic myoglobin and urate and thus further defend kidney function.

Bosentan improves renal regional blood flow in rats with experimental congestive heart failure

The effects of the mixed endothelin receptor antagonist bosentan on renal regional haemodynamics were investigated in rats with aorto-caval fistula, an experimental model of congestive heart failure. A matched group of normal rats served as control. Injection of bosentan (10 mg/kg i.v.) to the rats with decompensated congestive heart failure produced an increase in cortical (+20%) and medullary (+12%) blood flow, and a decrease in vascular resistance in the cortex (-30%) and medulla (-23%), while reducing mean arterial pressure by approximately 10 mm Hg. In rats with compensated congestive heart failure and in normal animals, infusion of bosentan did not affect blood pressure and cortical perfusion. These findings indicate that 1) endothelin receptor blockade produces beneficial effects on renal haemodynamics in rats with experimental congestive heart failure and 2) endothelin-1 may be involved in the pathogenesis of renal hypoperfusion only in decompensated congestive heart failure.

Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes

SummaryThe effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10−9−10−6 mol/l, which corresponds to concentrations found in the plasm of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect.

Hyperbaric oxygen treatment improves GFR in rats with ischaemia/reperfusion renal injury: a possible role for the antioxidant/oxidant balance in the ischaemic kidney

Background. Ischaemic kidney injury continues to play a dominant role in the pathogenesis of acute renal failure (ARF) in many surgical and medical settings. A major event in the induction of renal injury is related to the generation of oxygen-free radicals. Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischaemic events but not for ARF. Therefore, the present study examined the effects of HBO on kidney function and renal haemodynamics in rats with ischaemic ARF. Methods. Renal ischaemia was induced by unilateral renal artery clamping (45 min) in rats. Within 24 h following ischaemia, rats were treated twice with HBO of 100% O2 at 2.5 absolute atmospheres for 90 min each (+HBO). Untreated rats (−HBO) served as a control. Forty-eight hours later, GFR, RBF and endothelial-dependent vasorelaxation were measured. In addition, the immunoreactive staining of 4-hydroxy-2-noneal (4-HNE), a major product of endogenous lipid peroxidation, and superoxide dismutase (SOD) were assessed. Results. In the −HBO group, GFR was reduced by 94% compared with the untouched normal kidney (ischaemic: 0.06 ± 0.03 ml/min, normal: 1.02 ± 0.13 ml). In contrast, in the +HBO group, GFR of the ischaemic kidney (0.36 ± 0.07 ml/min) was reduced only by 68% compared with the contralateral normal kidney (1.12 ± 0.12 ml/min). In line with these findings, HBO improved the vasodilatory response to ACh as expressed in enhancement of both total and regional renal blood flow. In addition, HBO reduced the formation of 4-HNE by 33% and 76% and increased SOD by 30% and 70% in the cortex and outer stripe region of the medulla of the ischaemic kidney, respectively. Conclusion. HBO attenuates the decline in GFR following renal ischaemia, and improves endothelial-dependent vasorelaxation, suggesting that treatment with HBO may be beneficial in the setting of ischaemic ARF.

Early fluid resuscitation in patients with rhabdomyolysis

Extensive rhabdomyolysis is often lethal unless treated immediately. Early mortality arises from hypovolemic shock, hyperkalemia, acidosis and myoglobinuric acute kidney injury (AKI). Many individuals with rhabdomyolysis could be saved, and myoglobinuric AKI prevented, by early vigorous fluid resuscitation with ≥12 l daily intravenous infusion of alkaline solution started at the scene of injury. This regimen stabilizes the circulation and mobilizes edema fluids sequestered in the injured muscles into the circulation, corrects hyperkalemia and acidosis, and protects against the nephrotoxic effects of myoglobinemia and hyperuricosuria. This regime results in a large positive fluid balance, which is well tolerated in young, carefully monitored individuals. In patients with rhabdomyolysis caused by muscle crush syndrome, mortality has been reduced from nearly 100% to <20% over the past 70 years through utilization of this intervention. This Perspectives discusses the lifesaving and limb-saving potential of early vigorous fluid resuscitation in patients with extensive traumatic and nontraumatic rhabdomyolysis.

Differential Effect of Endothelin-1 on Renal Regional Blood Flow: Role of Nitric Oxide

Summary: This study evaluated the effects of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively) and the interactions with other local vasoactive systems in the regulation of renal regional blood flow. CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized Wistar rats. Administration of ET-1 (1.0 nmol/kg, i.v.) produced a decrease in CBF (δ= - 20%) and at the same time increased MBF (δ= +24%). In the presence of nitric oxide (NO) blockade by L-NAME, the vasodilatory effect of ET-1 on MBF was completely blocked and actually reversed (δ= - 19%), whereas the cortical vasoconstrictor effect was potentiated (δ = −31%). Cyclo-oxygenase inhibition with indomethacin attenuated the vasodilator effect of ET-1 on MBF (δ = + 12%) but did not affect the changes in CBF. Therefore, ET-1 exerts a differential effect on intrarenal regional blood flow, i.e., a decrease in CBF and an increase in MBF. The medullary vasodilator action of the peptide is dependent on an intact NO system and, to a lesser extent, on prostaglandin synthesis.

Modification of pulmonary metabolism of noradrenaline in experimental obstructive jaundice.

The pulmonary metabolism of noradrenaline (NA) was measured in lungs removed from 3 day sham-operated rats and from rats whose bile ducts had been ligated 3 days earlier (BDL). The pulmonary metabolism of NA as measured by a single clearance of the radio-labelled 14C-amine was significantly increased in lungs excised from BDL rats as compared to that measured in the sham-operated rats. The change in metabolism was associated with an alteration in the pulmonary uptake of NA and not with the activities of the enzymes monoamine oxidase types A and B and catechol-O-methyl transferase. Moreover, it was not correlated with rises in the bilirubin or cholesterol concentrations in the serum of the BDL rats and occurred independent of any changes in pulmonary pressure. In a second series of experiments, the evolution of this abnormality over the period of one to six days postoperative was investigated. In the sham-operated rats, there was no significant change in the pulmonary metabolism of NA even by the sixth day. In contrast, there were time-dependent increases from one to six days in these metabolic processes in BDL rats with the highest values being at six days. In contrast, the serum concentrations of bilirubin and cholesterol and activities of the enzymes, alanine transaminase and alkaline phosphatase all rose to their maximum by the fourth day and thereafter declined. Although serum albumin levels fell significantly in BDL rats they were not significantly different from sham-controls. Thus, change in pulmonary metabolism of NA with obstructive jaundice increases with time from one to six days and it not related to the blood chemical changes of biliary obstruction or hepatic synthetic function.

Isolated Adrenal Mineralocorticoid Deficiency Due to Amyloidosis Associated With Familial Mediterranean Fever

A patient with familial Mediterranean fever (FMF) associated with renal amyloidosis, presented with hyperkalemia and acidosis which were excessive to his moderate degree of azotemia. The cause of this abnormality was isolated hypoaldosteronism with otherwise normal adrenal function and tubular capacity to transport potassium. This selective involvement of the zona glomerulosa stands in marked contrast to the usual sparing of the glomerulosa seen in post mortem studies of patients with FMF and amyloidosis reported from this country.