Biomedical subjects

O Kohmoto

Publications and source records attributed to O Kohmoto.

42 records · Page 3Linked to original sources

PubMed1988

Alterations in cation homeostasis in cultured chick ventricular cells during and after recovery from adenosine triphosphate depletion.

Alterations in cation homeostasis during and after recovery from myocardial ischemia may account for some of the reversible and irreversible components of myocardial cell injury. To investigate possible mechanisms involved, we exposed cultured layers of spontaneously contracting chick embryo ventricular cells to media containing 1 mM cyanide (CN) and 20 mM 2-deoxyglucose (2-DG), and zero glucose for up to 6 h, and then allowed cultured cells to recover in serum-free culture medium for 24 h. Changes in Na, K, and Ca contents, 42K uptake and efflux, ATP content, cell water content, and lactate dehydrogenase (LDH) release were measured, and compared with changes produced by exposure to 10(-3) M ouabain and severe hypoxia. Exposure to CN and 2-DG caused marked increase in cell Na (sevenfold) and Ca (fivefold) contents, and a decrease in K content (one-fifth normal), coincident with ATP depletion to one-tenth normal levels. This produced only slight cell injury, evidenced by increased LDH release. Recovery for 24 h resulted in return to near normal values (expressed in nanomoles per milligram of protein) of Na, Ca, and ATP contents. However, there was failure of cell K content to return to normal, associated with a persistent reduced net uptake of 42K, and an increase in the rate of 42K efflux. These abnormalities in K homeostasis were associated with a decrease in cell volume and water content per milligram of protein. More marked ATP depletion (to 1/100 normal values) was produced by hypoxia plus 2-DG and zero glucose, and was associated with much more severe cell injury manifested by LDH loss. Ouabain exposure resulted in a much greater Ca gain (20-30-fold), relative to increase in Na content, than did either CN and 2-DG or hypoxia; and ouabain effects were not reversible (after a 15-fold or greater increase in Ca content was produced) and were associated with significant LDH release. We conclude that these cells are resistant to cell injury caused by moderately severe Ca overload and ATP depletion produced by exposure to CN and 2-DG. However, metabolic inhibition of ATP production produces persistent abnormalities in K homeostasis, associated with functional abnormalities.

Adenosine Triphosphate↗

PubMed1988

Effects of alpha human atrial natriuretic polypeptide on the systemic hemodynamics and coronary circulation in patients with ischemic heart disease.

Alpha human atrial natriuretic polypeptide (alpha-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 micrograms/kg/min for 15 min. During infusion of alpha-hANP, left ventricular (LV) systolic pressure decreased from 144 +/- 19 (SD) to 129 +/- 22 mmHg (p less than 0.01), LV end diastolic pressure (EDP) from 15 +/- 5 to 13 +/- 4 mmHg (p less than 0.05), mean aortic pressure from 102 +/- 14 to 91 +/- 14 mmHg (p less than 0.01), time constant of LV pressure fall (T) from 100 +/- 15 to 88 +/- 13 msec (p less than 0.05), systemic vascular resistance (SVR) from 1711 +/- 206 to 1424 +/- 340 dynes.sec.cm-5 (p less than 0.05) and coronary vascular resistance (CVR) from 8.5 +/- 1.2 to 7.4 +/- 1.3 x 10(4) dynes.sec.cm-5 (p less than 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r = 0.92, p less than 0.01), and the fall in CVR was approximately 68% of that in SVR. Increases occurred in heart rate from 63 +/- 7 to 66 +/- 8 beats/min (p less than 0.05), LV dp/dt from 1558 +/- 266 to 1627 +/- 238 mmHg/sec (p less than 0.05), LV dp/dt/p from 22.9 +/- 3.2 to 25.6 +/- 3.7/sec (p less than 0.01), and myocardial oxygen consumption (from 7.9 +/- 2.4 to 9.8 +/- 2.1 ml/min, p less than 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Plasma concentration of alpha-hANP and renal responses to alpha-hANP infusion in patients with congestive heart failure and those with chronic renal failure.

To study the role of alpha-human atrial natriuretic polypeptide (alpha-hANP) in body fluid regulation, we measured the plasma concentration of alpha-hANP and renal function in 9 patients with congestive heart failure (CHF), 10 with chronic renal failure (CRF) and 8 normotensives (NT) before and during alpha-hANP infusion at 0.025 microgram/kg.min. The plasma concentration of alpha-hANP was significantly higher in the CHFs and CRFs than in the NTs (319, 168 and 72 pg/ml, respectively). Alpha-hANP infusion decreased mean blood pressure in a similar manner in the 3 groups (-5%, p less than 0.01 each). Increases in urinary sodium excretion and glomerular filtration rate during alpha-hANP infusion, however, were greater in the CHFs and CRFs than in the NTs. Furthermore, the higher the preinfusion level of renal vascular resistance (RVR), the greater was the reduction in RVR by alpha-hANP (r = -0.80, p less than 0.001). The metabolic clearance rate (MCR) of alpha-hANP was significantly smaller in the CHFs and CRFs than in the NTs (38, 35 and 67 ml/min.kg, respectively). These results suggest that the renal vasodilatory actions of alpha-hANP seem to be enhanced in patients with increased RVR and that the elevation of the basal plasma concentration of alpha-hANP in CHFs and CRFs may be in part due to the low MCR.

Adult↗

PubMed1988

Acute hemodynamic effects of alpha human atrial natriuretic polypeptide in patients with congestive heart failure.

Acute hemodynamic and humoral effects of synthesized alpha human atrial natriuretic polypeptide (alpha-hANP, 0.025 microgram/kg/min for 40 min) on 6 patients with severe congestive heart failure were assessed. Plasma alpha-hANP concentration was high in patients and increased further (from 463 +/- 360 to 1,282 +/- 670 pg/ml, mean +/- SD, p less than 0.01) following alpha-hANP infusion, but plasma norepinephrine (1,030 +/- 865 to 971 +/- 785 pg/ml) was not changed. Increases in urine output (1.0 +/- 0.8 to 2.6 +/- 2.3 ml/min) and Na+ excretion rate (87 +/- 89 to 257 +/- 211 mEq/min/m2) were statistically insignificant. A significant reduction was induced in mean aortic pressure (99 +/- 25 to 96 +/- 26 mmHg, p less than 0.05), mean right atrial pressure (11 +/- 9 to 7 +/- 8 mmHg, p less than 0.01), mean pulmonary arterial pressure (39 +/- 13 to 33 +/- 12 mmHg, p less than 0.05) and mean pulmonary capillary wedge pressure (27 +/- 8 to 20 +/- 7 mmHg, p less than 0.01). Heart rate, cardiac index, systemic vascular resistance and pulmonary vascular resistance were not altered. In conclusion, alpha-hANP induced decreases in left ventricular filling pressure and rightside heart pressure which were attributed to venodilatation rather than natriuresis in patients with congestive heart failure. Preserved cardiac output with decreased preload suggested that alpha-hANP improved cardiac function.

Adult↗

PubMed1987

Plasma concentrations of alpha-human atrial natriuretic polypeptide and cyclic GMP in patients with heart disease.

Plasma concentrations of immunoreactive alpha-human atrial natriuretic polypeptide (i alpha-hANP) and cyclic guanosine monophosphate (cGMP) were measured in 70 patients with heart disease. Plasma concentrations of i alpha-hANP were directly related to the severity of heart disease (F = 29.61, p less than 0.001). Plasma concentrations of i alpha-hANP were well correlated with pulmonary capillary wedge pressure (PCWP; r = 0.64, p less than 0.001), mean pulmonary arterial pressure (PAP; r = 0.62, p less than 0.001), and mean right atrial pressure (RAP; r = 0.75, p less than 0.001). Plasma concentrations of cGMP were also directly related to the severity of heart disease (F = 13.61, p less than 0.001) and highly correlated with plasma concentrations of i alpha-hANP (r = 0.73, p less than 0.001). Plasma concentrations of cGMP were also closely correlated with PCWP (r = 0.69, p less than 0.001), mean PAP (r = 0.61, p less than 0.001), and mean RAP (r = 0.60, p less than 0.001). The i alpha-hANP concentrations of plasma samples obtained from the coronary sinus were approximately fourfold higher than those of samples obtained from the pulmonary artery, whereas cGMP concentrations were comparable in plasma samples obtained from either site. Elevation of cGMP concentrations following intravenous infusion of synthetic alpha-hANP was comparable in plasma samples obtained from the coronary sinus and the pulmonary artery. These findings suggest that elevated plasma concentrations of i alpha-hANP in cardiac patients result from an increase in the secretion of ANPs, which is probably accelerated by elevation of right or left atrial pressure, and that plasma concentrations of cGMP reflect circulating levels of alpha-hANP.

Adult↗

PubMed1987

Mechanisms of abnormal myocardial relaxation induced by ischemia: comparison of low flow ischemia and hypoxia in isolated rabbit heart.

To investigate the mechanisms of altered myocardial diastolic stiffness and relaxation induced by myocardial oxygen deficit, we compared the hemodynamic effects of low flow ischemia (myocardial infarction model) and hypoxia in which the coronary flow was not reduced (angina pectoris model) in isolated retrograde perfused rabbit hearts. A 15-min hypoxia induced a significant increase in the left ventricular end diastolic pressure (LVEDP 10 +/- 3 to 21 +/- 7 mmHg, p less than 0.05), Po (-6 +/- 6 to 12 +/- 5 mmHg, p less than 0.01) and TB (41 +/- 8 to 54 +/- 10 ms, p less than 0.05), where Po and TB are the asymptote and the time constant of the isovolumetric left ventricular pressure decline (P = Po + A e-t/TB), respectively. There was a close linear correlation between the delta Po and delta LVEDP (t = 0.98, p less than 0.01), and between delta TB and delta LVEDP (r = 0.73, p less than 0.05). Low flow ischemia increased Po (0 +/- 4 to 2 +/- 3 mmHg, p less than 0.05) and TB (43 +/- 4 to 50 +/- 11 mmHg, NS). When DPI 201-106, a cardiotonic agent, was given to the hypoxia moded by increasing the Ca++ sensitivity of contractile proteins, further increases were observed in LVEDP (to 25 +/- 8 mmHg, p less than 0.05) and Po (to 15 +/- 7 mmHg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗