Significance of right atrial function during right sided inotropic stimulation of pig hearts in situ.

Cardiac adjustments to inotropic stimulation of the right side of the heart were examined in anaesthetised, open chest pigs by calcium chloride infusion (80 mumol.min-1) into the right coronary artery. At stable haemodynamic conditions and at constant heart rate, right ventricular (RV) pre-ejection segment length increased by 4.6 (2.7-7.2) % (median, 95 % confidence interval) (p less than 0.01), RV end diastolic pressure rose from 5.3 (3.4-7.7) to 6.0 (3.6-8.8) mm Hg (p less than 0.05), and stroke volume rose by 6.8 (4.2-10.8) % (p less than 0.001). When the effect of right atrial contraction on RV filling was excluded by simultaneous pacing of atria and ventricles, the RV pre-ejection segment length no longer increased, and stroke volume rose by only 3.5 (0.1-9.5) % (p less than 0.05) during right side inotropic stimulation. Right atrial inotropic stimulation improves right ventricular filling, and may cause redistribution of blood from the systemic to the pulmonary circulation. This redistribution would raise the pulmonary vascular pressures, and thereby also improve left ventricular filling. The improved right ventricular filling partly accounts for the rise in RV output.

Cardiac adaptation to one hour of mild regional low flow ischaemia in the pig.

OBJECTIVE: The aim was to determine the cardiac consequences of a 1 h period of mild regional low flow ischaemia in the pig heart. METHODS: In eight pentobarbitone sodium anaesthetised pigs (weight range 23-38 kg), the mid left anterior descending coronary artery was constricted by a hydraulic occluder. Transmural coronary blood flow (Doppler flowmetry) was reduced to approximately 70% of control for 1 h. After complete release of the occluder cardiac function was monitored for 2 h. Left ventricular segment lengths were continuously recorded in the region subjected to low flow ischaemia and in a control region supplied by the circumflex artery. RESULTS: After 1 h with a 28(SEM 3)% reduction in coronary blood flow, the systolic shortening index decreased from 100 to 68(7) (p < 0.001). This index transiently normalised upon reperfusion. Thereafter it declined, reaching a nadir of 72(5) at 1.25 h of reperfusion, and subsequently improved to 82(6) at 2 h of reperfusion. CONCLUSIONS: Normalisation of local myocardial function appears during the first minutes of reperfusion after 1 h of mild low flow ischaemia and is followed by a period of stunning.

Sodium depletion increases platelet and plasma catecholamines in hypertensive men.

The catecholamine content in blood platelets is considerably higher than that in plasma, and platelet catecholamines must be taken up from plasma, since blood platelets lack enzymes for catecholamine synthesis. However, it is unknown whether platelets take up and store catecholamines during physiological in vivo increments in plasma catecholamines. Previously untreated 50-year-old men (n = 17) with mild to moderate essential hypertension were given a low sodium diet for 2 weeks. Urinary excretion of sodium decreased from 201 +/- 11 (SE) to 24 +/- 5 and 19 +/- 4 mmol/24 hr after 1 and 2 weeks, respectively. During the first week, the blood platelet concentration of norepinephrine increased from 27.2 +/- 2.9 to 39.6 +/- 4.7 pg/mg (p less than 0.005) and venous plasma norepinephrine increased from 3.7 +/- 0.4 to 5.6 +/- 0.5 pg/ml (p less than 0.005), and venous plasma dopamine increased from 26 +/- 4 to 41 +/- 5 pg/ml (p less than 0.05). During the second week, both plasma and platelet norepinephrine and dopamine remained elevated. Platelet epinephrine showed a small increase from baseline to the second week (p less than 0.05), but no concomitant increase in plasma epinephrine occurred. Thus, sodium depletion increases both platelet and plasma catecholamines and blood platelets may take up catecholamines in vivo. Platelet catecholamine content may be an integrated measure of plasma catecholamine concentrations during variations caused by sodium depletion.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased platelet and vascular smooth muscle reactivity to low-dose adrenaline infusion in mild essential hypertension.

During low-dose adrenaline infusion, platelet count, platelet size, plasma beta-thromboglobulin (BTG) and forearm vascular resistance (FVR) were measured in twelve 40-year-old men with mild, untreated hypertension. The average platelet count increased from 195 to 226 X 10(9)/l (P less than 0.001), platelet size from 7.31 to 7.53 X 10(-15)/l (P less than 0.01), BTG from 0.61 to 1.08 nmol/l (P less than 0.02) and FVR decreased from 97 to 58 (arbitrary units; P less than 0.001) during the infusion. The change in platelet count reflects splenic release of platelets, the change in plasma BTG reflects platelet release reaction, while the reduced FVR reflects vascular smooth muscle cell relaxation. In 11 normotensive men aged 40 years, platelet count increased from 187 to 201 X 10 g/l (P less than 0.01) during an equal low-dose adrenaline infusion. This increase in platelet count is significantly less than in the hypertensive group (P less than 0.01). There was statistically no significant change in platelet size, BTG or FVR in the normotensive group. Arterial adrenaline rose from 0.5 to 2.5 nmol/l in the hypertensive and from 0.5 to 2.4 nmol/l in the normotensive group. A third group of 12 normotensive men received saline infusion: neither platelet parameters nor FVR changed in this group. Thus, a small and equal dose of adrenaline elicited a greater increase in platelet count, an enhanced platelet release reaction and a more pronounced forearm vasodilation in hypertensive than in normotensive subjects.

Increased platelet size and release reaction in essential hypertension.

Basal platelet function was measured in 35 40-year-old men with untreated mild essential hypertension and compared with 44 age-matched normotensive men. The groups differed significantly with respect to platelet size in venous blood (hypertensive, 7.46 +/- 0.10 X 10(-15) l versus normotensive, 7.11 +/- 0.09 X 10(-15) l; P = 0.01) and arterial concentration of the platelet-specific protein beta-thromboglobulin (hypertensive, 1.11 +/- 0.23 nmol/l versus normotensive, 0.59 +/- 0.04 nmol/l; P = 0.02). The normotensive subjects had significantly higher beta-thromboglobulin (BTG) in venous than in arterial blood (P less than 0.01). The hypertensive men showed no such difference. In contrast to the normotensive subjects, the hypertensive group had reduced arterial compared with venous platelet count (P less than 0.01). This may reflect an increased liability in the hypertensive subjects to lose platelets through adherence to the cannula during arterial blood sampling. The above findings point to increased platelet activity in essential hypertension, particularly in arterial blood.

Does increased platelet release normalize during anti-hypertensive treatment?

Blood platelet function was evaluated in 10 men, all 50 years old, with untreated, mild hypertension. Each patient was examined four times: At the beginning of the study, after 5 weeks on placebo treatment, after the following 5 weeks on propranolol 160 mg daily, and finally after a second period of 5 weeks on placebo. At baseline the plasma level of the platelet release product beta-thromboglobulin (BTG) was 41.6 (30.5-57.0) micrograms/l (median and 95% confidence interval). During the first placebo period BTG was normalized to 21.0 (14.1-25.9) micrograms/l. While systolic blood pressure and heart rate fell during beta-adrenergic receptor blockade, BTG remained unchanged throughout the rest of the observation periods. Platelet size increased significantly during treatment with beta-blocker. The present study indicates that the normalization of elevated platelet function which previously has been reported to occur during anti-hypertensive drug therapy, may be explained by patient adaptation to the blood sampling procedure.

Effects of adrenaline infusion on platelet number, volume and release reaction.

At the end of a diagnostic right heart catheterization ten patients received an intravenous infusion of l-adrenaline which gradually increased the arterial plasma adrenaline concentration from resting physiological values to high values as seen during myocardial infarction, pheochromocytoma and hypoglycemia. Blood was sampled from the brachial artery, femoral vein and hepatic vein. During the adrenaline infusion venous beta-thromboglobulin concentrations increased 23% from 61 +/- 5 to 80 +/- 7 micrograms/l (mean +/- SE), arterial platelet counts 20% from 212 +/- 17 to 253 +/- 25 X 10(9)/l and arterial platelet volume 4% from 7.25 +/- 0.20 to 7.56 +/- 0.21 femtoliter. All changes were significant at the 5% level. Thus, acute increments of arterial plasma adrenaline significantly stimulated the blood platelet parameters studied.

Increased plasma noradrenaline during severe sodium restriction does not stimulate platelet release in essential hypertension.

Seventeen 50-year old hypertensive men, previously untreated with blood pressure 157 +/- 4/110 +/- 2 mmHg (means +/- SE) were given a low sodium diet for 2 weeks. During the second week, the diet was supplemented with potassium. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:4 and 1:11, respectively. Sympathetic noradrenergic tone increased considerably during the first week. Thus, venous plasma noradrenaline increased from 254 +/- 22 to 347 +/- 28 pg/ml (p less than 0.001) and arterial concentration from 253 +/- 36 to 317 +/- 42 pg/ml (n = 10, p less than 0.001). No significant change was observed in sympathetic adrenal tone as reflected by normal plasma adrenaline in venous (42 +/- 5 vs 43 +/- 6 pg/ml, ns) or arterial blood (71 +/- 10 vs 82 +/- 15 pg/ml, n = 10, ns) or in venous plasma concentration of the blood platelet release product beta-thromboglobulin (BTG) (50 +/- 8 vs 43 +/- 5 ng/ml, ns). During the second week sympathetic noradrenergic tone remained highly significantly elevated compared to baseline but still no change in plasma adrenaline or plasma BTG was found. Thus, whereas sodium depletion did increase plasma noradrenaline concentration markedly in these hypertensive men, no change in adrenaline concentration was observed, and blood platelet release reaction was unchanged. Plasma noradrenaline within the physiological concentration range does not seem to serve as a regulator of in vivo platelet function.

Older adults and the news media: utilization, opinions, and preferred reference terms.

We surveyed 868 community-dwelling older adults about their (a) utilization of media news, (b) opinion of news media coverage of older people, and (c) preferences among terms used by news media to refer to senior citizens. Those with more than high school education read more newspaper news than those with less education. All groups watched TV news more frequently than they read the newspaper. Respondents had reservations about the news media's accuracy in, attitude toward, and interest in stories regarding seniors. Clear education and gender-related patterns emerged, whereas age proved nonsignificant in many analyses. Respondents' preferred reference terms were: (nouns) senior citizen, retiree, senior, and older adult; (adjectives) retired, senior, and mature. Respondents disliked: (nouns) old man/woman, old person, oldster, old timer, and geezer; (adjectives) old, aged, gray, and geriatric.

The concentration of protein-compounds in interstitial tissue of patients with chronic critical limb ischaemia and oedema.

BACKGROUND: Many of chronic critical limb ischaemia (CLI) patients have distal leg and foot oedema. Previous electronmicroscopic studies have shown that chronic severe ischaemia may cause hypoxic damage of the capillary endothelium, including morphological changes i.e. multiplicated/thickened basal lamina, and formation of interendothelial gaps. To assess the functional consequences of these morphologic derangements, where proteins can leak through, we investigated the composition of the interstitial fluid in oedematous ischaemic limbs. PATIENTS AND METHODS: Nine female and 3 male patients with a mean age of 79 +/- 7.9 years were included. All had unilateral CLI and peripheral pitting oedema. Leg and foot volume was measured with water displacement volumetry. Blister suction technique was used to collect subcutaneous interstitial fluid. The concentration of albumin, transferrin, immunoglobulin G and alpha 2-macroglobulin in plasma and blister fluid was measured by immunoturbidimetry. Nine patients, 8 women and 1 man with a mean age of 83 +/- 5.5 years with a proximal femur fracture served as an age-matched control group. RESULTS: The mean concentration of albumin in blister fluid was significantly lower in the patients, whereas the mean concentration of alpha 2-macroglobulin in blister fluid did not differ between patients and controls. Mean ratio between concentrations in blister and serum of albumin, transferrin and immunoglobulin G in the limbs with CLI and oedema were significantly lower than respective values in the control group. However, there was no significant difference in the ratio of alpha 2-macroglobulin between these groups. CONCLUSION: A higher transcapillary concentration gradient for proteins in CLI limbs signifies an increase in the net osmotic pressure gradient across the capillary wall, which may be a potential oedema limiting factor.

Hyper-responsiveness to low-dose epinephrine infusion in mild essential hypertension.

The present study was undertaken to evaluate the effects of intravenous infusion of small amounts of epinephrine on haemodynamics, renal electrolyte excretion and blood platelets in essential hypertension. Arterial plasma epinephrine concentrations were increased during the infusion to approximately 2.5 nmol/l both in a group of 40-year-old men with untreated mild essential hypertension (blood pressure 154 +/- 3/100 +/- 3 mmHg, n = 12) and in a group of age-matched male controls (124 +/- 3/78 +/- 2 mmHg, n = 11). In the hypertensive group only, mean blood pressure decreased, forearm blood flow increased, forearm vascular resistance decreased (P less than 0.001 for all) and the urinary excretion of sodium and potassium increased (P less than 0.01 for both). The hypertensive group also responded with an increase in plasma beta-thromboglobulin (P less than 0.05), blood platelet size (P less than 0.05) and a higher increase in platelet counts than in the normotensive group (P less than 0.05). Thus, in several ways the hypertensive patients showed a hyper-responsiveness to amounts of epinephrine which corresponds well to the plasma concentration achieved during psychological and physical activity.

Increased arterial adrenaline is highly correlated to blood pressure and in vivo platelet function in pre-eclampsia.

Compared with normotensive pregnant women (n = 13), patients with severe pre-eclampsia (n = 13) had increased arterial plasma adrenaline (P < 0.001), peripheral venous adrenaline (P < 0.01), arterio-venous differences of adrenaline (P < 0.001) and venous concentration of the platelet release product beta-thromboglobulin (P < 0.001). In the pre-eclamptic group, arterial adrenaline correlated with mean blood pressure (r = 0.90, P < 0.001), heart rate (r = 0.78, P < 0.01) and beta-thromboglobulin (r = 0.82, P < 0.001), while in the normotensives adrenaline correlated only with beta-thromboglobulin (r = 0.76, P < 0.01). According to these results, sympathetic adrenal tone is increased in pre-eclampsia and may play a role in the pathogenesis of high blood pressure and platelet activation in this disease.

Cardiac adjustments to left-side inotropic stimulation of in situ pig hearts.

Cardiac adjustments to inotropic stimulation of the left side of the heart by continuous infusions of isoproterenol (0.6-0.8 microgram/min) and calcium chloride (240 mumol/min) into the left coronary artery were examined in open-chest pigs (17-36 kg) anesthetized with pentobarbital sodium. Both agents caused a reduction in the left ventricular (LV) preload and preejection segment length (PESL). Stroke volume (SV) rose by only 1.2 ml from 15.9 ml (P less than 0.01) during isoproterenol infusion, but when the reduction in LV PESL of 3.2% (P less than 0.01) was restored by saline infusion, SV increased by 27%. The LV PESL reduction was less at hypervolemia than at normovolemia. A computer-based model of the circulation predicted most of these changes and suggested redistribution of blood from the pulmonary to the systemic circulation. During isoproterenol infusion, the pulmonary arterial pressure fell, and the right ventricular end-ejection segment length declined. Reduced right ventricular afterload thus appears to be an important mechanism by which right ventricular output is increased during a selective increase in LV inotropy.

Role of adenosine for reactive hyperemia in normal and stunned porcine myocardium.

The role of adenosine for reactive hyperemia in normal and stunned myocardium was examined in 16 open-chest barbiturate-anesthetized pigs. Interstitial adenosine concentration was reduced or enhanced by intracoronary infusion of adenosine deaminase or the nucleoside transport inhibitor R 75231, respectively. In normal myocardium, adenosine deaminase reduced volume of hyperemia (Doppler flowmetry) after a 30-s left anterior descending coronary artery (LAD) occlusion by 20% (6-34%; P < 0.05), whereas R 75231 increased volume of hyperemia by 15% (2-24%; P < 0.05). Adenosine deaminase reduced volume of hyperemia after a 2-min LAD occlusion by 27% (13-37%; P < 0.001), whereas R 75231 increased volume of hyperemia by 66% (53-159%; P < 0.001). Adenosine deaminase and R 75231 did not affect maximal hyperemia. Volume of hyperemia after a 2-min LAD occlusion was reduced in stunned myocardium (%systolic segment length shortening reduced by approximately 45%, ultrasonic technique) but not further altered by either adenosine deaminase or R 75231. These findings show that adenosine contributes to reactive hyperemia after 30-120 s of ischemia in normal myocardium and indicate that the reduced reactive hyperemia in stunned myocardium is due to reduced accumulation of adenosine during ischemia.