Significant Increase In Pulse Pressure Research Articles

Serum levels of Nitric Oxide metabolites in relation to Body Mass Index and Arterial stiffness in young individuals

Introduction: Obesity is a multi-factorial disorder defined as abnormally high levels of body fat accumulation. It is a major emerging pandemic of this century which can be attributed to alterations in eating habits, lifestyle choices and rise in sedentary behaviour. The activation of pro-inflammatory signalling pathways linked to obesity can result in vascular endothelial dysfunction and changed levels of Nitric oxide (NO). Hyperlipidaemia may exacerbate arterial stiffness which is a precursor to atherosclerosis. In this study, we tried to evaluate the changes in levels of nitric oxide in obese individuals and its association with arterial stiffness. Objectives: To identify the association of serum levels of Nitric oxide metabolites with Body Mass Index (BMI) in apparently healthy subjects. To evaluate any correlation between serum nitric oxide metabolites, BMI and arterial stiffness in obese individuals. Result: The results showed a significant increase in systolic blood pressure (p<0.001) and no change in diastolic blood pressure and significant increase in pulse pressure(p<0.001) with increase in visceral adiposity (Waist Circumference) more than BMI. Results of Pearson correlation indicated that there is a significant small negative relationship between BMI and Serum NO levels, (r =- 0.534, p <.001). There was significant increase in Brachial ankle Pulse Wave Velocity (Ba PWV) (p=0.001) and Carotid Femoral Pulse Wave Velocity (CF PWV) (p=0.01) in obese subjects when compared to controls. Conclusion: Our study results showed that abdominal obesity more than overall obesity is more strongly associated with decreased serum NO levels and increased arterial stiffness. In obese individuals, increased arterial stiffness as reflected by increased pulse wave velocity may contribute to predicting cardiovascular disease in both genders in addition to development of hypertension.

Differences in cardiovascular function comparing prior preeclamptics with nulliparous controls.

The objective of the current study was to evaluate cardiovascular function; including blood pressure, cardiac output, pulse wave velocity and vascular compliance in nonpregnant nulliparous women compared to women with a history of preterm preeclampsia. This was a case control study. Blood pressure was measured using the Finapres Pro. Baseline cardiac output was determined by echocardiography. Pulse wave velocity was estimated using simultaneous electrocardiographic tracings and ultrasound determined arterial flow waveforms and calculated as estimated distance divided by the time interval between EKG r-wave peak and ultrasound derived peak popliteal artery flow. During volume challenge, 500mL of lactated Ringers solution was infused through an indwelling antecubital catheter over 10min. Cardiac output and blood pressure during and 15min after the infusion were estimated using the Finapres Pro. Indices of arterial stiffness and vascular compliance. Previous preeclamptics exhibited a significant increase in pulse pressure and cardiac output in response to volume challenge when compared with nulliparous controls. Prior preeclamptics had a strong positive correlation between blood pressure indices (r=0.50-0.68, p⩽0.01) and pulse pressure (r=0.58, P=0.008) with pulse wave velocity that was not evident in control women. In women with prior preterm preeclampsia a relationship between blood pressure, intravascular volume and arterial stiffness, is evident in the nonpregnant state and in the absence of hypertension or overt cardiovascular disease. This supports an overarching hypothesis that nonpregnant physiology is an important contributor to pregnancy adaptations.

Reduced Common Carotid Artery Blood Flow in Spontaneously Hypertensive Rats is Unaffected by Aging and/or Chronic In Vivo Resveratrol Treatment

This study examined common carotid artery (CCA) blood flow (using a perivascular flowprobe) and pressure (using a catheter‐tip transducer) in anesthetized Adult (20‐24 wk old) and Aging (60‐70 wk old) Wistar Kyoto rats (WKY) and Spontaneously Hypertensive rats (SHR) following 28‐days of in vivo treatment (in drinking water, ab libitum) with either no trans resveratrol (RSV; No‐RSV), a moderate RSV dose (Mod‐RSV; ~0.075 mg/kg/day; to mimic daily red wine consumption), or a high RSV dose (High‐RSV; ~7.5 mg/kg/day). CCA mean, maximal systolic, minimum diastolic, and pulse pressure, and heart rate, were all significantly elevated in SHR vs. WKY (p<0.01). Aging was associated with a significant increase in pulse pressure in WKY (p<0.01). CCA mean, maximal systolic, and minimum diastolic blood flow, and vascular conductance, were all significantly reduced in SHR vs. WKY (p<0.05). Aging did not have a significant effect on the flow parameters in either SHR or WKY. Neither Mod‐RSV nor High‐RSV treatment had a significant effect on the CCA blood pressure and blood flow variables measured. These data demonstrate that the reduction in CCA blood flow found in SHR is unaffected by aging or chronic in vivo RSV treatment. Further investigation into what can account for and alter the reduced CCA blood flow found in SHR is warranted.Funded by NSERC.

Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats.

An increase in pulse pressure (PP) is highly associated with hypertension. The goal of this study was to determine the effect of increased aortic stiffness on PP and endothelial dysfunction as precursors to hypertension. A rat model of suddenly increased aortic stiffness by use of a nonconstrictive restraint (glue coating) on aortic surface was created to investigate the change of PP and mean arterial pressure (MAP). Group I (n = 16) underwent aorta restraint for 4 wk. Group II (n = 12) underwent aortic restraint for 4 wk, followed by restraint removal to evaluate extent of reversibility for additional 4 wk. The aortic and peripheral endothelial function was assessed by ACh-stimulated endothelium-dependent vasodilation. The level of nitrate/nitrite (NOx), endothelin-1 (ET-1), and prostacyclin (PGI2) were measured in the serum and artery tissue. We found that aortic stiffening causes a significant increase in PP and MAP (P < 0.05). The endothelial function was markedly blunted (P < 0.05) in both aorta and small peripheral artery. After removal of the restraint, the impaired endothelium function persisted in the aorta likely due to sustained deterioration of aortic wall, but was partially restored in peripheral artery. The endothelial dysfunction was correlated with a decrease in NOx and PGI2 (P < 0.05) and an increase in ET-1 (P < 0.05). Our results show that aortic stiffening results in widening of PP, which affected endothelium function through changes in synthesis of NOx, ET-1, and PGI2. These findings suggest that increased aortic stiffness may be a cause of increased PP and a precursor to hypertension.

Reduced carotid artery blood flow of spontaneously hypertensive rats is unaffected by aging from 20 weeks (young adulthood) to 65 weeks (upper middle age) (LB690)

The objective of this study was to quantify blood flow (using a perivascular flowprobe) and pressure (using a catheter‐tip transducer) in the common carotid artery (CCA) of anesthetized young adult (~20 week old) and upper middle aged (~65 week old) Wistar Kyoto rats (WKY) and Spontaneously Hypertensive rats (SHR). In young adult SHR vs. WKY, mean (172±10 vs. 82±2 mmHg), systolic (198±13 vs. 92±4), diastolic (151±9 vs. 72±5), and pulse pressure (48±5 vs. 20±2), and heart rate (371±12 vs. 277±19 beats/min), were each elevated (p&lt;0.01). In SHR, aging had no effect on these pressure parameters, or heart rate; whereas, in WKY, aging was associated with a significant increase in pulse pressure (31±1 mmHg; p=0.04) but no other pressure parameter. Mean (4.94±0.29 vs. 3.80±0.54 ml/min), maximum systolic (11.58±1.08 vs. 19.00±2.18), and minimum diastolic blood flow (0.62±0.73 vs. 1.90±0.34) were each reduced in young adult SHR vs. WKY (p&lt;0.05), while flow pulsatility was no different (3.23±0.73 vs. 3.43±0.44). Aging had no effect on these flow parameters in either SHR or WKY. Together, these data demonstrate that CCA blood flow is &gt;20% reduced in young adult SHR, and that this reduction is neither exacerbated nor attenuated at upper middle age. Given the important contribution of the internal branches of the CCAs to the total perfusion of the brain, these findings may be of pathophysiological and clinical relevance.Grant Funding Source: Supported by NSERC Canada

Vascular remodeling and media calcification increases arterial stiffness in chronic kidney disease

Background: Cardiovascular disease is the most common cause of death in patients with chronic kidney disease (CKD). Arterial stiffness and calcification are non-traditional risk factors of cardiovascular disease in CKD. In CKD rats, we investigated the involvement of smooth muscle cells differentiation to osteoblast-like cells and blood vessel wall remodeling, associated with media calcification, in arterial stiffness.Method: CKD with vascular calcification was induced by subtotal nephrectomy followed by treatment with a high calcium and phosphate diet, and vitamin D supplementation (Ca/P/VitD). At week 3–6, hemodynamic parameters and pulse wave velocity (PWV) were assessed. Vascular media calcification and remodeling were determined by histological von Kossa staining and confocal immunofluorescence analysis of osteocalcin, elastin, α-smooth muscle actin (α-SMA) and collagen-1.Results: Treatment of CKD rats with Ca/P/VitD, but not normal animals, induced a significant increase in pulse pressure and PWV (p < 0.05) and marked calcification in the media. In calcification areas, de novo expression of osteocalcin was observed, whereas α-SMA immunofluorescence levels were reduced (p < 0.01). The immunofluorescence levels of elastin were also reduced, which was related to disruption of elastic lamella. In contrast, collagen-1 immunofluorescence levels in areas of calcification were increased (p < 0.01). Changes in both α-SMA and elastin inversely correlated with the PWV.Conclusion: This study indicate that smooth muscle cells differentiation to osteoblast-like cells and the associated media remodeling, which includes disruption of elastic lamellas and deposition of collagen are, at least in part, associated with the increased arterial stiffness observed in CKD rats with vascular calcification.

Abstract 206: PPARγ Deficiency Causes Aortic Stiffness and Dysregulated Elastin Turnover

PPARγ, a nuclear receptor that regulates adipocyte development and glucose homeostasis, is the molecular target of a class of insulin-sensitizing drugs. Loss-of-function mutations in PPARG gene are implicated in human hypertension and PPARγ agonists decrease blood pressure both in animal models and human patients. We have previously generated mice with varying Pparg expression created by modifying its 3′-UTR sequence, and concluded an inverse relationship between PPARγ expression level and blood pressure. Interestingly, mice with extremely low PPARγ expression exhibited an increase in systolic blood pressure without significant change in diastolic blood pressure, ultimately causing a significant increase in pulse pressure. Thus, we hypothesized that PPARγ deficiency impairs aortic elasticity, resulting in the increase in pulse pressure. Aortic pulse wave velocity (PWV) was significantly increased in PPARγ hypomorphic mice, suggesting that aortas of PPARγ hypomorphic mice were stiffer than those of wild-type mice. The measurement of mechanical property by atomic force microscope (AFM) showed higher tissue rigidity in the aorta of PPARγ hypomorphic mice. Expression of elastin in aortas was significantly decreased, and negatively correlated with aortic PWV in PPARγ hypomorphic mice. This was accompanied by increased elastin fiber breaks, elastolytic activity, and expressions of MMP-9 in aortas of PPARγ hypomorphic mice. The elevated PWV in PPARγ hypomorphic mice was ameliorated after treatment of PPARγ agonist. Together, our results suggest that PPARγ deficiency impairs elasticity in aorta and underscore the importance of PPARγ in the regulation of blood pressure and vascular reactivity.

Prenatal nicotine exposure induces gender-associated left ventricular-arterial uncoupling in adult offspring.

Alterations in vascular or myocardial structure and function have been demonstrated in offspring subjected to prenatal nicotine exposure (PNE), however, limited data are available on how these changes interact. The present study assessed the hypothesis that prenatal nicotine exposure induced gender-specific alterations of left ventricular-arterial coupling indices in adult offspring. Female Sprague-Dawley rats were exposed to either nicotine (8 mg/kg/day) or saline via subcutaneous osmotic mini-pumps throughout gestation. Male and female offspring, aged 12 months, underwent non-invasive echocardiography and invasive left ventricular cannulation. Left ventricular-arterial coupling was analysed as the ratio of effective arterial elastance (Ea) to ventricular end-systolic elastance (Ees). The left ventricular myocardium and aorta were stained with hematoxylin and eosin and the myocardial cell cross-sectional area was calculated. Simultaneously, the ratio of medium thickness to internal diameter in the aorta and mesenteric artery was determined. The fibrosis component of left ventricle myocardium was analyzed by Sirius-red staining and further confirmed by hydroxyproline determination. The elastic properties of the aortic wall were analyzed by van Gieson staining. PNE caused significant increases in pulse pressure (56.36 ± 7.41 vs. 50.16 ± 4.94 mmHg; P<0.05) and left ventricular meridional wall stress (78.25 ± 9.12 vs. 69.64 ± 7.58 kdyne/cm(2); P<0.05) in male offspring compared with the control. Conversely, no similar effect was observed in female offspring. An elevated augmentation index was noted in male and female pups. Additionally, Ea/Ees was reduced in PNE males compared with control males, due to a disproportionate increase in Ees vs. Ea whereas in females, Ea/Ees did not differ significantly due to tandem increase in Ea and Ees. In addition, collagen cross-linking was markedly higher in male offspring, whereas it was unaltered in females compared with their respective controls. Fragmentation of the elastic network in the aorta and the increased ratio of medial thickness to internal diameter in the mesenteric artery were more evident in male offspring when compared with female offspring. PNE caused combined ventricular-arterial stiffening in male and female offspring, with lower Ea/Ees in males, while Ea/Ees was preserved in females. Enhanced collagen cross-linking in the myocardium, underdeveloped elastic fibers in the aorta and remodeled resistance vessels were associated with pathological ventricular arterial mismatching. The results of the present study indicated that male offspring were more susceptible to the development of ventricular and arterial dysfunction in response to PNE compared with female offspring.

Differential Effects of Vitamin D Analogs on Vascular Calcification

We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio. Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification. We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease. Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments. We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings.

Cardiovascular Effects of Hyperhomocysteinemia in Conscious Unrestrained Rats

Experiments were designed to determine whether hyperhomocysteinemia (Hhe) affects cardiovascular function when monitored in conscious unrestrained animals. Adult, male Sprague-Dawley rats were fed a homocystine-supplemented diet for 6 months. Blood pressure (BP), heart rate, and pulse pressure were monitored continuously, 24 h a day, using biotelemetry techniques. The resulting intermediate level of Hhe was not associated with significant changes in heart rate, diastolic BP, systolic BP, or the circadian variation in heart rate. In spite of the lack of significant changes in systolic and diastolic BP, there was a slight but statistically significant increase in pulse pressure after 4 months of treatment that returned toward control levels after 6 months. Current results indicate that Hhe alone does not have significant effects on BP. Furthermore, they suggest that the previously reported Hhe-induced adverse cardiac remodeling and diastolic dysfunction in this animal model are not the result of pressure overload.

Warfarin Therapy and Systolic Hypertension in Men With Atrial Fibrillation

Warfarin decreases the activity of matrix Gla-protein and causes extensive arterial calcification leading to increased systolic blood pressure (SBP) and pulse pressure (PP) in rats. We performed post hoc analyses of the Stroke Prevention in Non-Rheumatic Atrial Fibrillation (SPINAF) trial, aiming to analyze the effects of warfarin on SBP and PP. The SPINAF trial was a randomized, double-blind, placebo-controlled trial comparing warfarin and placebo in 525 subjects with nonrheumatic atrial fibrillation. After exclusions for inadequate follow-up, 284 subjects with average treatment lasting 23.7 months were available for analysis (144 given placebo and 140 warfarin). Baseline SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), and PP were 132 +/- 18, 81 +/- 9, 98 +/- 11, and 50 +/- 16 mm Hg in the warfarin group, and 133 +/- 21, 80 +/- 13, 97 +/- 14, and 54 +/- 15 mm Hg in the placebo groups (all P values, NS). There was no statistically significant difference between the placebo and warfarin groups in any of the BP parameters at any time point. However, stratified analyses showed a significant increase in PP in warfarin-treated subjects with a history of hypertension (4.9 +/- 13.1 mm Hg v 0.2 +/- 11.9 mm Hg in the placebo group, P = 0.022), and those with baseline SBP > or =140 mm Hg (4.8 +/- 18.9 mm Hg v -3.4 +/- 11.2 mm Hg in the placebo group, P = .038). A similar trend was noted in diabetic subjects but it was not statistically significant. Based on the study results, treatment with warfarin does not result in increased BP in men with atrial fibrillation. However, it is possible that subjects at higher baseline cardiovascular risk may be more susceptible to the chronic effects of warfarin on arterial hemodynamics.

Pulse Pressure and Cardiovascular Events in Postmenopausal Women With Coronary Heart Disease

Pulse pressure (PP) has been shown to predict risk for cardiovascular events in men; however, this association has not been well established in women. Hormone replacement therapy may improve arterial compliance, but findings from cross-sectional and prospective studies report inconsistent results. We sought to examine the relationship between PP and risk for cardiovascular events, and to determine the effect of hormone therapy on PP in postmenopausal women with coronary heart disease (CHD). A total of 2,763 postmenopausal women (mean age, 66 +/- 7 years [+/- SD]) with CHD in the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled, secondary CHD prevention trial of estrogen plus progestin, were followed up on average for 4.1 years. BP was measured at baseline and annually. Mean baseline PP was 62 +/- 16 mm Hg. There were 361 myocardial infarctions (MIs) or CHD deaths, 265 hospitalizations for congestive heart failure (CHF), and 215 strokes or transient ischemic attacks (TIAs). Women in the highest quartile of PP at baseline had a 47% increase in risk for MI or CHD death and more than a twofold increase in risk for stroke and TIA events or hospitalization for CHF (p < 0.01 for each outcome). After adjustment for other cardiovascular risk factors and mean arterial pressure, PP remained significantly associated with incident stroke or TIA events (odds ratio, 1.25; p = 0.02) and hospitalizations for CHF (odds ratio, 1.31; p < 0.01) but not with MI or CHD death. After adjustment for diastolic BP, systolic BP was similarly associated with stroke or TIA (odds ratio, 1.30; p < 0.01) and hospitalized CHF (odds ratio, 1.30; p < 0.01) and was also weakly associated with risk for MI and CHD death (odds ratio, 1.18; p = 0.02). Mean PP was 1- to 2-mm Hg higher in women randomized to hormone replacement therapy vs those receiving placebo (p < 0.01). PP had predictive value for CHF and stroke or TIA, but not MI or CHD death in this cohort of postmenopausal women with CHD. Use of hormone replacement therapy produced a small, statistically significant increase in PP. Further research is necessary to determine the clinical utility of PP as a potential therapeutic target.

Ambulatory blood pressure profile after carotid endarterectomy in patients with ischaemic arterial disease

To assess the circadian blood pressure profile observed 3 months after endarterectomy. Twenty-five patients undergoing unilateral or bilateral carotid endarterectomy were compared with a control population of 20 patients, matched for age, sex, weight and drug therapy. Casual mean blood pressure measured by mercury sphygmomanometry was similar in both groups. Non-invasive ambulatory blood pressure monitoring showed that, whereas mean arterial pressure was identical in both groups, the group undergoing surgery had a significant increase in pulse pressure and its variability over 24 h. Such abnormalities predominated during the nocturnal period, in which the reduction in systolic blood pressure was less pronounced in the operated group than in controls. For all parameters there was no significant difference between subjects with unilateral or bilateral endarterectomy. This study provides evidence that patients with carotid endarterectomy were characterized in the long term by an increase in the pulsatile component of blood pressure and its variability, in association with a disturbance in the physiological circadian rhythm. Such findings were not identified using casual blood pressure measurements.

Haemodynamic effects of the calcium facilitator Bay K‐8644 in rats following vascular calcium overload

1. The haemodynamic effects of the Ca2+ facilitator Bay K-8644 (Bay) were studied in a model of calcinosis induced by acute treatment with vitamin D3 and nicotine administration over 4 days with 13 days of recovery. 2. Calcium content of the left ventricular myocardium increased 8-9 fold, while aortic Ca2+ levels increased up to 12-fold in treated animals. There were minimal changes in the ECG and no change in the level of plasma alpha-hydroxy-butyrate-dehydrogenase, a cardiac specific enzyme which increases during ischaemia. Significant increases in pulse pressure (PP) were seen in anaesthetized and conscious calcinotic rats, with no increase in cardiac output index (DABF) or systemic vascular resistance. However, aortic rigidity (AORI) was significantly elevated in the calcinotic group under anaesthesia. 3. In both control and calcinotic rats, pressor responses to i.v. Bay were exclusively mediated by an increase in aortic blood flow (DABF) as lower body vascular resistance (TLBVR) did not change. The increase in DABF at low doses (0.1-1 microgram kg-1) of Bay probably resulted from an increase in venous return induced by the agonist, as Bay had little effect on cardiac contractility over this dose range (as estimated by left ventricular dp/dtmax) and did not cause tachycardia. At higher doses (10-1000 micrograms kg-1), Bay significantly increased LV dp/dt. Bay caused dose-related increases in AORI in pithed calcinotic rats, but a decrease in AORI in control animals. 4. The calcinosis model, which incorporates a recovery period to obviate the acute effects of nicotine and/or vitamin D3 treatment, results in long-term tissue calcium accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Intra-Aortic Balloon Counterpulsation for the Treatment of Ischemic Stroke

Colloid volume expansion has been shown to increase cerebral blood flow to ischemic brain in an animal stroke model and improve recovery in patients. It is, however, potentially hazardous to use in older patients because of frequently associated cardiovascular disease. Intra-Aortic Balloon Counterpulsation might reduce the risks of using volume expansion therapy in the elderly patient. This study was designed to see if Intra-Aortic Balloon Counterpulsation (without volume expansion), in an animal with a normal heart, would increase cerebral blood flow and EEG activity in the ischemic brain. Unilateral cerebral ischemia was produced in baboons (n = 9) after right middle cerebral artery occlusion. A 12 ml intra-aortic balloon catheter was introduced into the descending aorta via the femoral artery prior to middle cerebral artery occlusion. The balloon was positioned distal to the origin of the left subclavian artery and following middle cerebral artery occlusion was inflated with each R wave on the ECG. Cardiac output, cerebral blood flow (by Hydrogen wash-out), computer-mapped EEG, and hemodynamic data were collected prior to middle cerebral artery occlusion and following occlusion both before and during counterpulsation. Intra-Aortic Balloon Counterpulsation produced a significant increase in pulse pressure from 54.7 ± 21 to 70.6 ± 33 mmHg (p = .043). No significant change was seen in cardiac output, mean arterial pressure, or cerebral blood flow. Although the computer- mapped EEG improved and the right (ischemic) hemisphere cerebral blood flow did increase slightly from 16.9 ± 6.5 to 18.3 ± 8.3 ml/100 gm/min, the cerebral blood flow changes were not significant (p=.295). It is possible that the desired increase in cerebral blood flow was not achieved partly because the animals were only 3-4 years old and were difficult to stroke. We believe that there is merit to a follow-up study in older primates with colloid volume expansion where Intra-Aortic Balloon Counterpulsation is used to protect the heart from the deleterious effects of volume expansion and where the cardiac effects of volume expansion and counterpulsation are quantified. Perhaps volume expansion with Intra-Aortic Balloon Counterpulsation will be safer and more effective than either treatment modality alone. (All data reported as mean ± standard deviation)

Modification of cardiovascular dynamics in orthostatic dysregulation in childhood by oxilofrin

In 10 children with clinically and hemodynamically proven orthostatic dysregulation of the sympathetic type, non invasive hemodynamics using sphygmographic techniques as well as systolic time intervals were evaluated. Measurements were taken during 10 minutes in the supine and a 65 degrees position on a tilting table before and after acute administration of Oxilofrin, 20 mg as well as after 2 and 4 weeks of chronic treatment with 20 mg t.i.d. During orthostatic stress, Oxilofrin caused a significant increase in pulse pressure, cardiac output, stroke volume, and systolic ejection rate with a reduction in peripheral vascular resistance compared to control. Pre-ejection period and isovolumic contraction time, while prolonged on baseline orthostatic stress, were only slightly shortened by Oxilofrin. These hemodynamic actions of the drug are explained by a stimulation of adrenergic beta and alpha receptions with the consequence of decreasing venous capacitance and increased venous return, thus providing a useful hemodynamic profile for the treatment of orthostatic dysfunction.

The augmentor action of the sympathetic cardiac nerves.

An augmentor action of the cardiac sympathetic nerves is demonstrated to elicit profound elevations in systolic blood pressure. Diastolic pressure does not rise in an equivalent amount and significant increase in pulse pressure occurs. This persists for a considerable time after removal of the stimulation. During stimulation of the left cardiac sympathetic, an augmentor action is often not accompanied by acceleration. Stimulation of the right cardiac sympathetic evokes both effects. The elevation of blood pressure is chiefly produced by augmentation of ventricular beats, not by cardiac acceleration.