Urinary electrolyte excretion after frusemide, amiloride and a combination of these drugs: an open, crossover study.

Urinary volume and electrolyte excretion were monitored for 24 hours in 12 elderly, catheterized patients with mild congestive cardiac failure. Five timed collections (0 to 3, 3 to 6, 6 to 9, 9 to 12 and 12 to 24 hours) were made after single doses of 40 mg frusemide, 5 mg amiloride and a combination tablet containing both 40 mg frusemide and 5 mg amiloride. Patients received each therapy according to a Latin Square design, with a 6-day washout phase separating the three study periods. The study periods consisted of a 24-hour control urinary collection, immediately followed by diuretic and a further 24-hour urine collection. Diuretics were not administered immediately prior to the study or during the washout phases. Amiloride, as expected, showed mild diuretic and natriuretic properties, but in the 12 to 24-hour period it induced a greater diuresis (p less than 0.05) than did frusemide or the combination. Frusemide and the combination tablet both produced a rapid and powerful diuresis in the 0 to 3-hour post-dose period and did not differ significantly in urine output at any time point. However, a difference in natriuretic activity was seen between frusemide and the combination, with the latter producing a significantly greater sodium excretion in the 12 to 24-hour period (p less than 0.05). Potassium-retaining activity throughout the 24 hours was marked after amiloride, with potassium excretion being significantly less (p less than 0.05) than either control, frusemide or the combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterisation of the excitation-contraction coupling system of the hypothermic myocardium following ischaemia and reperfusion.

The excitation-contraction coupling system of the globally ischaemic, hypothermic myocardium (60 min at 10 to 16 degrees C; I, n = 7) was studied by evaluating the functional integrity of the sarcoplasmic reticulum (SR) and the myofibrils (M). Comparison was made to the identical model followed by reperfusion (R, n = 7) and to sham-operated, time-matched controls (C, n = 7). Calcium uptake velocity from both the 60 min ischaemic group (I) and the reperfusion group (R) was significantly depressed (c = 0.960 +/- 0.05, I = 0.535 +/- 0.033, R = 0.662 +/- 0.035 micromolCa2+ . mg-1 . min-1, P less than 0.01). In contrast, SR . CA2+-ATPase activity was not affected by the hypothermic, ischaemic process (C = 1.150 +/- 0.08, I = 1.338 +/- 0.199 mumol Pi . mg-1 . min-1) but exhibited a small, significant depression after reperfusion (R = 0.940 +/- 0.04 mumol Pi . mg-1 . min-1, P less than 0.05). Myofibrillar pCa-ATPase curves in both experimental groups were significantly depressed (maximal ATPase activity: C = 0.18 +/- 0.01, I = 0.125 +/- 0.005, R = 0.115 +/- 0.01 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilising double reciprocal plots, demonstrated an increase in injury in the hypothermic myocardium results from a breakdown of those subcellular structures responsible for the maintenance of the excitation-contraction coupling system. The ischaemic period, rather than reperfusion seems to be the major contributing factor in this sequence of pathological events.

Excitation-contraction coupling in hypothermic ischemic myocardium.

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.