摘要:

To study transmembrane electrophysiological properties of blood-perfused mammalian heart cells during normal perfusion and during acute ischemia, 1- to 2-mm cubes of neonatal hamster atrial and ventricular myocardium were transplanted to the adult hamster cheek pouch and studied with microelectrodes 4–7 days later, when vascularization and spontaneous contractions occurred. Action potentials recorded from the transplants were similar to those recorded from neonatal and adult hamster myocardium studied in vitro. Interrupting blood flow to spontaneously beating transplants reduced diastolic depolarization and suppressed automaticity. After automaticity ceased, the transplants were paced with a bipolar electrode or intracellular microelectrode. Action potential amplitude, resting potential, and dV/dtmaxdecreased during ischemia. Action potential duration and the intracellular current threshold for excitation increased initially, subsequently decreased to values less than control, and increased again prior to the onset of inexcitability. Conduction delay and block occurred during the late stages of ischemia. Depressed action potentials recorded during ischemia were suppressed by tetrodotoxin (10−5M) but not by verapamil (2 × 10−6M). These data indicate that: (1) the electrophysiological properties of cheek pouch cardiac transplants are normal, (2) ischemia suppresses transplant automaticity, (3) cellular excitability increases during the early stages of ischemia and decreases at a time when conduction delay and block occur, and (4) action potentials generated during the later stages of ischemia appear to be depressed fast responses, rather than slow responses.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We used the synthetic progestin R5020 (17α,21-dimethyl-19-norpregna-4,9-diene- 3,20-dione) to characterize cytoplasmic progesterone receptors in baboon(Pupiosp.) aorta and myocardium. The relative ability of selected steroids to inhibit binding of radiolabeled R5020 to aortic cytoplasmic progesterone receptors was radioinert R5020, 1.0; progesterone, 0.31; triamcino- lone acetonide, 0.06; testosterone, 0.002; estradiol-17β, 0.01; and cortisol, 0.001. The relative ability of these same steroids to inhibit binding of radiolabeled R5020 to myocardial cytoplasmic progesterone receptors was, respectively, 1.0, 0.58, 0.21, 0.01, 0.01, and 0.001. Both aortic and myocardial cytoplasmic progesterone receptors migrated as macromolecules with a sedimentation coefficient of 8–9S on low ionic strength linear sucrose gradients. Cytoplasmic binding of R5020 was inactivated by incubation at 37°C. Saturation analysis at 2°C showed aorta and myocardium, respectively, contained 41.6 ± 16.1 (mean ± SD) and 14.0 ± 2.8 fmol R5020 binding sites/mg cytosol protein. The dissociation constant for R5020 was 2.8 ± 1.2 nm, aorta, and 2.0 ± 1.1 nM, myocardium. The presence of progesterone receptors in baboon cardiovascular tissues suggests that progestins may directly influence cardiovascular tissue function.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Studies in rat and dog hearts examined the hypothesis that the cardiac adenosine pool contains an intracellular compartment. Enzymatically dispersed rat cardiocytes contain 70 pmol adenosine/mg protein which is resistant to 10 U/ml adenosine deaminase (ADA). Incubating dog heart homogenates for 1 minute at 37°C with 10 U ADA/mL did not change adenosine levels perceptibly from the average control value of 1.28 nmol/g. Studies employing [3H]hypoxanthine arabinoside as an adenosine surrogate showed that this nucleoside penetrates into pericardia! superfusates, attaining concentrations equal to those in blood plasma by 30 minutes. Since blood, cardiac interstitium, and pericardial superfusate are three compartments in series, this validates the use of pericardial superfusates equilibrated for ⩾30 min as probes of cardiac interstitial composition. In eight dogs, pericardial superfusate adenosine concentration averaged 0.24 μM. Cardiac muscle adenosine content averaged 0.87 nmol/g, indicating that the interstitial compartment accounts for only 6% of the cardiac pool. Dog cardiac muscle contains a [3H]adenosine binding protein whose size, affinity for adenosine analogs, and ability to synthesize S-adenosylhomocysteine (AdoHcy) suggest it is S-adenosylhomocysteine hydrolase (SAH). Studies employing a dog erythrocyte model show that adenosine is bound to a protein in this cell; treatment with L-homocysteine greatly reduces the amount of adenosine recovered. The half-time for the dissociation of [3H]adenosine from SAH at 37°C is 2.5 hours, and in the presence of ADA is >6 hours. Thus, although adenosine bound to SAH can serve as a substrate for AdoHcy synthesis, this experiment does not support the idea that the dissociation of adenosine occurs to a physiologically significant extent. Thus, we are uncertain of the functional role of the intracellular adenosine compartment.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Isolated single vascular muscle cells were used for studies of the inherent norepinephrine sensitivity and the conditions important for detecting highest norepinephrine sensitivity. Rat vascular muscle cell contractions were quantitated from spontaneous contractions during pulse applications of the drugs, with a time course designed to simulate norepinephrine release in situ. Isolated vascular muscle cells showed a sensitivity to norepinephrine two orders of magnitude greater than those found from isolated intact blood vessels. Associated with the high sensitivity, there was a marked reduction in the response to a second application of norepinephrine or phenylephrine. The reduced second response appears to result from desensitization that is more pronounced in cells that have been exposed to only trace concentrations of catecholamines. These data appear to suggest that there might be continuous suppression of transmitter sensitivity that occurs as a result of transmitter exposure, and possibly cell-to-cel! associations. Desensitization would at first severely limit the response to norepinephrine by reducing or eliminating the response to prolonged exposure or a second dose. Thereafter, a lessening of the desensitization process on continuous exposure to catecholamines would be the result, in part, of lowered sensitivity and, in part, of a smaller desensitization response. This process would continuously modulate norepinephrine sensitivity, based on the frequency and extent of stimulation, and we have called it the theory of physiological desensitization.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The alterations in local cerebral glucose utilization in 58 anatomically discrete regions which occur during a period of hemorrhagic hypotension have been investigated in conscious rats, using the quantitative autoradiographic14C-deoxyglucose technique. Hemorrhagic hypotension (mean arterial pressure reduced by approximately 50 mm Hg) effected significant increases in glucose utilization in eight areas of the central nervous system, namely, the nucleus of the tractus solitarius (glucose utilization increased by 38%), the dorsal motor nucleus of the vagus (by 36%), locus coeruleus (by 38%), lateral habenular nucleus (by 40%), periventricular nucleus of the hypothalamus (by 41%), paraventricular nucleus of the hypothalamus (by 97%), supraoptic nucleus (by 86%), and the interstitial nucleus of the stria terminalis (by 84%). In five of these eight areas (nucleus of the tractus solitarius, dorsal motor nucleus of the vagus, paraventricular and supraoptic nuclei, and the interstitial nucleus of the stria terminalis), a significant relationship could be demonstrated between the level of glucose utilization and mean arterial blood pressure. In the majority of the CNS regions examined (neocortex, hippocampus, thalamus, extrapyramidal and motor areas), hemorrhagic hypotension was without significant effect upon local cerebral glucose utilization. The results provide direct evidence of the functional involvement of specific brain areas of conscious rats (thus obviating complicating anesthetic influences) in the response of the CNS to hemorrhagic hypotension.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Developmental aspects of fetal adrenal and vascular responses to endogenous increase in plasma angiotensin II (All) following sequential reductions of fetoplacental blood volume were studied in two groups of chronically catheterized fetal lambs (seven were <120 days and seven were >130 days of gestation, term being 145 days). At similar levels of hemorrhage, the rise in plasma renin activity (PRA) was found to be greater in fetuses >130 days than in those <120 days (P< 0.025). Similarly, the effect of hemorrhage on plasma All was more pronounced in fetuses >130 days than in those <120 days (P< 0.05). No changes in plasma aldosterone were seen during hemorrhage in fetuses <120 days, whereas plasma aldosterone increased (P< 0.001) in those >130 days. This increase correlated with the rise in plasma All (r = 0.70,P< 0.001). In order to determine whether factors other than the rise in plasma All were responsible for the increase in plasma aldosterone in fetuses >130 days, these results were compared to results obtained in four nephrec- tomized fetuses >130 days submitted to similar degrees of hemorrhage. No changes in PRA or plasma All were observed. However, a small increase in plasma aldosterone (from 31 ± 13 to 47 ± 11 pg/ml,P< 0.01) was found, and this correlated with changes in plasma potassium concentration (r = 0.50,P< 0.05). Finally, mean arterial blood pressure decreased during hemorrhage in fetuses <120 days (P< 0.05), whereas no changes were observed in those >130 days unless their kidneys were removed. This suggests that the renin-angiotensin system is an important modulator of fetal blood pressure during hemorrhagic stress.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Changes in stimulation rate alter the electrical and mechanical characteristics of myocardial cells. We have investigated the possibility that intracellular sodium activity (aNa) changes with stimulation and correlates with changes in contraction strength. Two kinds of liquid membrane Na+-selective microelectrodes were used to measure aNain guinea pig and sheep ventricular muscle and in sheep Purkinje strands. Stimulation produced a rate- and time-dependent elevation of aNa. Small increases in aka were seen at stimulation rates as slow as 0.2 Hz, and faster rates of stimulation elevated aNaby over 30%. The changes seen in Purkinje strands and ventricular muscle were similar. Following a period of stimulation, aiNa and Vmreturned to their pre-stimulus levels with the same time courses. This is consistent with the suggestion that the post-stimulation hyperpolarization is the result of an increased rate of electrogenic Na+extrusion. The effects of stimulation on a L and tension were compared with those of ouabain. The comparison suggests that rapid stimulation could produce increased contraction strength as the result of a substantial gain in intracellular calcium via a Na-Ca exchange mechanism, but that this is only one of several factors determining the forcefrequency relationship.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We have examined the feasibility of determining coronary collateral blood flow in an open-chest dog by a “load line” type of analysis as is often employed to analyze transistors and vacuum tubes. The load line equation states that collateral flow is given by the quantity: where POP is peripheral coronary pressure, AOP is aortic pressure, Qretis retrograde flow, and K is a constant. The validity of this equation was critically tested in a series of dog experiments in which the collateral vessels were found to approximate a linear resistance, the source pressure for the collaterals (K in the equation) was found to be 0.8 of aortic pressure, and the retrograde flow with zero back pressure was found to account for all of the collateral flow. Finally, we found that estimates from the equation correlated well with direct microsphere measurements of collateral flow. All of these findings support the use of the proposed technique which determines collateral flow by three easily measured laboratory parameters.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The study was performed to determine whether there is a structural vascular abnormality in normotensive subjects with hypertensive relatives. We examined maximal vasodilator capacity of forearm resistance vessels in 23 normotensive young men (mean blood pressure 94 ± 0.4 mm Hg, mean ± SE) with hypertensive relatives (age 24 ± 0.1 years) and in 17 normotensive subjects (mean blood pressure 85 ± 0.4 mm Hg) with no family history of hypertension (age 24 ± 0.1 years). Maximal vasodilator capacity was examined by measuring minimal vascular resistance during peak reactive hyperemia after release from 10 minutes of arterial occlusion. Minimal forearm vascular resistance after release from 10 minutes of arterial occlusion was 25% higher (P< 0.02) in subjects with hypertensive relatives (2.0 ± 0.02 units) than that in subjects with no family history (1.5 ± 0.01 units). We confirmed the previous findings that increasing metabolic vasodilator stimulus by performing intermittent handgrip exercise during 10 minutes of arterial occlusion did not augment peak dilation. This suggests that 10 minutes of arterial occlusion produced maximal vasodilation. Forearm vascular responses to ice on the forehead was greater in subjects with hypertensive relatives than those in subjects with no family history. These results suggest that there may be a structural abnormality in the forearm resistance vessels in normotensive subjects with family history of hypertension.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

This study examined the effects of nitroglycerin and nifedipine on the transmural distribution of myocardial blood flow when ischemia-induced vasodilation of the distal coronary vasculature caused a proximal coronary stenosis to become flow-limiting. Studies were performed in chronically instrumented awake dogs with electromagnetic flowmeter probes and hydraulic occluders on the left circumflex coronary artery. Myocardial blood flow was estimated with 15|i radioactive microspheres. During control conditions, subendocardial (endo) flow significantly exceeded subepicardial (epi) flow (endo:epi = 1.33 ± 0.12). Following a 10-second coronary occlusion, reactive hyperemia occurred with excess arterial inflow resulting in 330 ± 37% blood flow debt repayment. This response was not altered by nitroglycerin (0.015 mg/kg, iv), but was decreased by nifedipine (0.01 mg/kg, iv) to 175 ± 38%, indicating depression of the coronary vasodilator response to a brief ischemic stimulus. When, following a 10-second occlusion, arterial inflow was limited to the preocclusion rate by a proximal stenosis, subepicardial flow increased at the expense of hypoperfusion of the subendocardium (endo/epi decreased to 0.50 ± 0.04;P< 0.01), and the continuing subendocardial ischemia resulted in augmentation of the subsequent reactive hyperemia (debt repayment = 556 ± 5%;P< 0.01). Both nitroglycerin and nifedipine abolished the augmentation of the reactive hyperemic response which occurred when a total occlusion was followed by an interval of coronary stenosis. This effect was associated with enhanced subendocardial blood flow during the interval of restricted inflow, suggesting that both of these agents alleviate the subendo- cardial hypoperfusion and ischemia which occur in the presence of a proximal flow-limiting coronary stenosis.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID