Left ventricular mass and blood pressure during ergometric exercise in primary hypertension

The pathophysiology of left ventricular hypertrophy (LVH) in hypertensive patients is still an intriguing point. The lack of a close relationship between LVH and systolic or diastolic blood pressure at rest, previously observed by other investigators, was confirmed in our group of 45 patients with uncomplicated primary hypertension. The strength of correlation between echocardiographic left ventricular mass (LVMe) and blood pressure, expressed as incremental area (IA = total area under the curve--basal area), however, increased during bicycle exercise testing (r = 0.33, p less than 0.05 for diastolic blood pressure; r = 0.39, p less than 0.01 for systolic blood pressure; r = 0.41, p less than 0.01 for mean arterial pressure). Other echocardiographic parameters of myocardial mass such as LVM index (LVMI) and septal thickness (ST) were also significantly correlated with blood pressure during exercise. These results suggest either that blood pressure during exercise is a better index of the cardiac workload than resting blood pressure or that the pathogenesis of cardiac hypertrophy involves an enhanced reactivity to adrenergic drive, particularly stimulated during ergometric exercise. Increased blood pressure alone, however, only partly accounts (about 20%) for the increase in myocardial mass in hypertensive patients; other factors, therefore, need to be further investigated for a better understanding of the pathophysiology of left ventricular hypertrophy.     

Beer Affects Oxidative Stress due to Ethanol in Rats

The relationship between chronic moderate beerconsumption and oxidative stress was studied in rats.Animals were fed three different isocaloric diets forsix weeks: a beercontaining diet (30% w/w), an ethanol-supplemented diet (1.1 g/100 g, thesame as in the beer diet) and an alcohol-free basaldiet. At the end of the feeding period, rats wereanalyzed for plasma and liver oxidative status. Somelivers were isolated and exposed toischemiareperfusion to assess the additional oxidativestress determined by reperfusion. No significantdifferences in plasma antioxidant status were foundamong the three dietary groups. Lipoproteins from the beer group,however, showed a greater propensity to resist lipidperoxidation. Ischemia caused a decrease in liver energyand antioxidant status in all groups. Nevertheless, ATP was lower in the livers of rats exposed tothe ethanol diet. During reperfusion, lipoperoxidationincreased significantly in all groups. However, liversobtained from ethanoltreated rats showed the higher formation of lipoperoxides. Inconclusion, a moderate consumption of beer in awell-balanced diet did not appear to cause oxidativestress in rats; moreover, probably through its minorcomponents, beer could attenuate the oxidative action ofethanol by itself.     

Radionuclide analysis of peak filling rate, filling fraction, and time to peak filling rate. Response to supine bicycle exercise in normal subjects and patients with coronary disease

Using gated equilibrium radionuclide angiography, variables of diastolic filling were analyzed at rest and during supine bicycle exercise in normal subjects (Group 1, n = 18), coronary patients with normal resting ejection fractions (Group 2, n = 26), and coronary patients with reduced resting ejection fractions (Group 3, n = 8). Indexes analyzed were peak filling rate and filling fraction during the first third of diastole. At rest, the peak filling rate was significantly lower in coronary patients than in normal subjects (3.18 +/- 0.82 end-diastolic volume [EDV]/s in Group 1 versus 2.41 +/- 0.66 EDV/s in Group 2, p less than 0.005; and 1.34 +/- 0.26 EDV/s in Group 3, p less than 0.001 versus Group 1). These differences persisted at peak exercise. Coronary patients also had significantly lower filling fractions at rest and during exercise than did normal control subjects. The time from end-systole to peak filling rate was longer at rest in patients in Group 2 (203 +/- 52 ms) than in subjects in Group 1 (172 +/- 50 ms, p less than 0.025). This remained true when the time to peak filling was normalized by the R-R interval. Although the exercise time to peak filling was longer in coronary patients in both Groups 2 and 3 than in Group 1, these differences were not apparent when the interval was normalized by the R-R interval. Thus, abnormalities in peak filling rate and filling fraction exist in patients with coronary disease both at rest and during exercise, but large overlaps exist between normal and coronary patients. Caution is advised in comparing the timing of events during diastole because apparent group differences may be related in part to rest or exercise heart rate.     

Differential effects of feeding on the ultradian variation of the growth hormone (GH) response to GH-releasing hormone in normal subjects and patients with obesity and anorexia nervosa

Nutritional status and metabolic fuels are factors involved in the regulation of GH secretion and GH responses to GHRH. The effects of feeding on GHRH-induced GH release were studied in 13 normal women, 14 obese women, and 9 women with anorexia nervosa. GHRH-(1-44) (50 micrograms, iv) was administered at 0900 h after an overnight fast or at 1300 h after a normal meal at 0800 h, and at the same times 45 min after a 800-Cal meal on different days. The mean peak plasma GH responses to GHRH administered before a meal at 0900 h were 52.8 +/- 5.6 (+/- SE) micrograms/L in normal women, 8.2 +/- 1.3 micrograms/L in obese women, and 53.2 +/- 7.7 micrograms/L in anorexic women. When GHRH was administered before a meal at 1300 h, the mean peak plasma GH levels were lower than those at 0900 h; this reduction was -64.2% in normal women, -64.9% in obese women, and -55.8% in women with anorexia nervosa. After feeding, the plasma GH responses to GHRH were blunted in normal women at 0900 h (-60.9%) and 1300 h (-34.6%) compared with the fasting peak responses. In obese women the plasma GH response to GHRH after feeding was increased compared with that when these women had fasted (+60% at 0900 h and +406.9% at 1300 h). Finally, differential effects of feeding were present in anorexic women; the response was lower at 0900 h (-46.4%) and greater at 1300 h (+50.8%). We conclude that there is an ultradian variation in GHRH-stimulated GH secretion and that the responses differ according to nutritional status and body weight.     

Determination of coronary flow reserve by parametric imaging

Nine mongrel dogs were instrumented with electromagnetic flow probes (EMF) to measure coronary blood flow through the left anterior descending (LAD) and left circumflex (LCx) coronary arteries at rest and after maximal coronary vasodilation (1 mg/kg/min adenosine). Relative coronary blood flow was determined by parametric imaging in the left posterior oblique projection using digital subtraction angiography (DSA). Transmural myocardial perfusion of the LAD and LCx beds was determined with tracer-labeled microspheres. Coronary flow reserve (maximal coronary blood flow divided by resting blood flow) was calculated under control conditions and after constriction of the proximal LAD or LCx by a screw occluder. Heart rate decreased significantly from 140 beats/min at rest to 122 beats/min after adenosine (p less than 0.001) and from 134 (rest) to 120 beats/min (adenosine; p less than 0.05) after coronary constriction. Peak systolic pressure was kept constant with an aortic constrictor. Left ventricular end-diastolic pressure increased significantly from 18 mm Hg at rest to 23 mm Hg (p less than 0.05) after coronary constriction. At baseline, coronary flow reserve was 4.2 with DSA, 3.8 with EMF, and 3.7 with microspheres; after coronary constriction, it was 2.6 (DSA), 1.9 (EMF), and 1.5 (microspheres) (all p less than 0.001 versus baseline). Coronary blood flow showed a good correlation between EMF and microspheres (r = 0.87, p less than 0.001), with a standard error of estimate (SEE) of 0.78 ml/g/min. Coronary flow reserve also showed a good correlation between EMF and microspheres (r = 0.82, p less than 0.001), with an SEE of 0.93. There was a moderate correlation between EMF and DSA (r = 0.68, p less than 0.001), with an SEE of 1.35 (40% of mean coronary flow reserve). The correlation coefficient between microspheres and DSA was 0.54 (p less than 0.01), with an SEE of 1.46 (39% of mean coronary flow reserve). The mean difference (accuracy) and standard deviation of difference (precision) were 0.2 +/- 1.0 between EMF and microspheres, -0.1 +/- 1.4 between EMF and DSA, and -0.6 +/- 1.7 between microspheres and DSA. We conclude that determination of coronary flow reserve by parametric imaging is associated with large variations that are greater than variations also inherent in the two reference techniques. Parametric imaging allows relatively accurate assessment of coronary flow reserve (small mean difference), but precision is low (large standard deviation of mean differences).(ABSTRACT TRUNCATED AT 400 WORDS)     

Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: a retrospective evaluation of 50 patients

The objective of this study was to investigate the relationship between growth hormone (GH) dynamic tests (thyrotropin-releasing hormone [TRH] test and oral glucose tolerance test [OGTT]), insulin-like growth factor-I (IGF-I) plasma values, tumor size, and clinical outcome in patients with GH-secreting pituitary adenomas. Furthermore, we investigated the potential prognostic utility of the above biochemical parameters in the follow-up of patients with acromegaly. We studied 50 acromegalic patients (18 males and 32 females; mean age, 40 years; range, 16 to 69) who underwent trans-sphenoidal removal of a GH-secreting pituitary adenoma from 1990 to 1994. Preoperatively, we evaluated (1) GH plasmatic levels after an oral glucose load (OGTT) (blood samples were drawn at -15, 0, 30, 60, 90, 120, 150, and 180 minutes after oral administration of 0.75 g/kg body weight [BW] of glucose), (2) GH plasma levels after a TRH test (200 microg as an intravenous [IV] bolus), and (3) basal IGF-I plasma levels after an overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and urinary free cortisol. The same tests were performed every year for 5 years. All of the patients were classified into 4 subgroups according to the system of Hardy and Vezina. Preoperatively, "controlled" patients (n = 29) had a GH paradoxical response to TRH (n = 28) and an unresponsiveness to OGTT (n = 29); 23 of them belonged to the I and II classes. Only 5 poorly controlled patients (n = 21) showed a preoperative paradoxical response to TRH and 9 had a preoperative GH partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our data suggest that in the preoperative period in acromegalic patients the simultaneous presence of a GH paradoxical response to TRH and lack of GH inhibition after OGTT is inversely related to the tumor size and therefore more likely to be restored to normal by surgical treatment.     

Paradoxical growth hormone response to thyrotropin-releasing hormone in acromegaly. Clinical correlations and prognostic value

We have investigated the effect of TRH on the release of GH in 20 acromegalic patients (14 females and 6 males) before and after selective removal of a pituitary tumour via transsphenoidal route. The follow-up period was 8 years. Pre-operatively the paradoxical response was present in 15 patients (75%). Mean GH values in TRH responders were significantly lower than in non-responders. According to the size and expansion diffusion of the adenoma, the patients were divided into 3 classes. The percentage of paradoxical response in patients in class III was significantly lower than in the other two classes. Postoperatively, mean GH values in pre-operative TRH responders were significantly lower than in non-responders; among 15 responders, 13 (86%) had postoperative GH levels under 5 micrograms/l; among 5 non-responders only 2 (40%) had GH values under 5 micrograms/l. Postoperatively 8 patients still had GH responsiveness to TRH: 6 with GH levels persistently (follow-up 8 years) under 5 micrograms/l and 2 with elevated GH values. The other 7 patients, who were responders pre-operatively and non-responders postoperatively, persistently exhibited low GH levels, except one subject who showed an increase in GH levels with reappearance of the paradoxical response, two years after surgery. These results suggest: 1. the paradoxical response may be expressed only when the hypothalamus-pituitary interactions are intact; 2. the disappearance of the paradoxical response cannot surely suggest a remission, and 3. the presence of a pre-operative paradoxical response is a good prognostic feature.     

Cardiopulmonary exercise variables in diastolic versus systolic heart failure

The response to cardiopulmonary exercise (CPX) in patients with heart failure (HF) with normal left ventricular (LV) ejection fractions (EFs) is not well characterized. To determine if CPX testing could distinguish between patients with HF with normal EFs (>50%; i.e., diastolic HF) and those with decreased EFs (> or =50%; i.e., systolic HF), CPX responses were compared between 185 patients with systolic HF (79% men, mean age 62.6 +/- 10.9 years) and 43 with diastolic HF (54% men, mean age 67.4 +/- 9.8 years) enrolled in a phase II multicenter clinical trial. All patients were evaluated with echocardiography and a standardized CPX test as part of the trial. CPX variables, including oxygen uptake at peak exercise (peak VO(2)) and the slope of the ventilation/carbon dioxide production ratio (VE/VCO(2)), were determined and analyzed by core laboratory personnel. Echocardiographic measurements included the LV EF, the E/A ratio, filling time, cavity volumes, right ventricular function, and mitral regurgitation. Patients in the diastolic HF group tended to be older (p <0.08), with more women (p <0.006) and with greater body mass indexes (p <0.02), than those in the systolic HF group. There was no significant difference in the use of beta blockers or the incidence of coronary artery disease. Patients with diastolic HF had decreased E/A ratios (0.9 +/- 0.4 vs 1.4 +/- 1.1, p <0.02, diastolic HF vs systolic HF) and increased filling times (30.4 +/- 3.2 vs 26.5 +/- 4.7 ms, p <0.01, diastolic HF vs systolic HF). No significant differences in peak VO(2) (14.4 +/- 1.9 vs 15.6 +/- 3.2 ml/kg/min, p = 0.06, diastolic HF vs systolic HF) were observed. The VE/VCO(2) ratios for the 2 groups were abnormal and comparable (32 2 +/- 7.5 vs 34.0 +/- 8.3, p = 0.3, diastolic HF vs systolic HF). In conclusion, the CPX response in patients with diastolic HF and systolic HF is markedly abnormal and indistinguishable with regard to peak VO(2) and ventilation despite marked differences in the LV EF.     

Periovulatory plasma prolactin response to synthetic growth hormone-releasing hormone in normal women

Following the demonstration of a positive prolactin (PRL) response to growth hormone-releasing hormone (GHRH) in acromegalic and anorexic women, we have injected GHRH (50 micrograms intravenously as a bolus) in normal women during various phases of their menstrual cycle in order to establish whether a positive response was present also in normal subjects. Synthetic GHRH 1-44 elicited a significant increase in circulating PRL levels in eight women studied during the periovulatory phase of the menstrual cycle. In contrast, no significant changes in circulating PRL levels after GHRH administration were found in nine women during the midfollicular phase or in five women during the midluteal phase. A temporal correlation between the midcycle gonadotropin peak and the positive response to GHRH has been observed. Synthetic GHRH elicited the expected increase in GH levels during all phases of the cycle studied. Our data demonstrate that GHRH is capable of stimulating a PRL response in normal subjects and raise the possibility that PRL secretion is regulated by several hormones of hypothalamic origin.     

Comparison of two-dimensional echocardiography, angiocardioscintigraphy and cineventriculography in the study of left ventricular wall motion in ischemic cardiopathy

Thirty-two patients with non acute myocardial infarction (inferior in twenty, anterior in ten, anterior and inferior in two) were studied with contrast left ventriculography, two-dimensional echocardiography and radionuclide angiography to assess left ventricular wall motion. We adopted the CASS criteria for the standard left ventriculography, and the Mayo Clinic classification for the echocardiographic study. Radionuclide angiography studies were obtained in left anterior oblique view; the images were evaluated with the use of Walsh-Hadamard transform; the left ventricle was divided in basal and apical septal, apical, posterolateral, posterobasal and two central segments. We tried to correlate the findings of the three techniques both for single segments and larger regions made of contiguous segments. Left ventricular angiography and two-dimensional echocardiography showed a fair concordance for both anterobasal and posterolateral left ventricular wall, whereas for the septal, apical and posterolateral regions contrast and radionuclide angiography had the best correlation. Compared to left ventricular angiography two-dimensional echocardiography shows better sensitivity than radionuclide angiography; the latter is more specific in defining left ventricular wall motion. The two non invasive techniques are therefore helpful in the evaluation of wall motion and their role is complementary.