Cardiac hypertrophy in hypertension. Repolarization abnormalities elicited by rapid lowering of pressure.

In hypertension, coronary flow is augmented and oxygen balance is adequate despite an increase in coronary resistance. For the maintenance of flow in the presence of and after regression of ventricular hypertrophy, the ratio of pressure and ventricular mass must remain normal. Coronary reserve would be altered if treatment normalized pressure but not ventricular mass or if pressure were lowered too fast. We investigated 42 patients with primary hypertension. In 28 (Group I) left ventricular mass index (by ultrasound) was within the mean value +2 SD (96 + 38 g/m2) of 145 controls and exceeded these values in the remaining 14 patients (Group 2). The diastolic pressure was lowered rapidly to between 85 and 90 mm Hg with two potent vasodilators, nifedipine (sublingually) and nitroprusside, while a 12-lead electrocardiogram was recorded continuously. During both tests, seven patients in Group 2 (responders) showed inversion of normal T waves, in lead I, aVL, and V3-6. These changes waxed and waned in parallel with the pressure fall and recovery and were not attributable to alterations in adrenergic tone, conduction disturbances, variations, or group differences in the QRS axis, QTc interval, heart rate, left ventricular fractional shortening, wall stress, rate of dimension increase in early diastole, or isovolumic relaxation. A ""steal phenomenon'' or passive collapse in compliant coronary lesions during vasodilatation seems unlikely; in fact, patients were free from coronary symptoms, and the electrocardiographic alterations occurred only in seven patients in Group 2, who had a greater left ventricular mass index and required a larger pressure drop to return the diastolic pressure to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.

OBJECTIVE: Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect. METHODS: These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism. RESULTS: The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition. CONCLUSIONS: These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.

Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension.

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.

Exercise performance in patients with uncomplicated essential hypertension. Effects of nifedipine-induced acute blood pressure reduction.

In untreated patients with uncomplicated essential hypertension, exercise induces an abnormal increase in blood pressure; the influences of this increase on exercise were evaluated by a cardiopulmonary exercise test (CPX) performed in control conditions (step 1) and during acute blood pressure reduction (step 2). Patients were classified as (1) normotensive (resting diastolic blood pressure [BPd] less than 90 mm Hg; n = 14), (2) mildly hypertensive (BPd of 90 to 104 mm Hg; n = 9), and (3) moderately to severely hypertensive (BPd greater than or equal to 105 mm Hg; n = 16). For the three groups, peak mean blood pressure during exercise was 125 +/- 5 mm Hg (mean +/- SEM), 144 +/- 3 mm Hg (p less than 0.01 vs normotensive), and 161 +/- 4 mm Hg (p less than 0.01 vs normotensive and p less than 0.01 vs mild hypertension), respectively. Oxygen consumption (VO2) at peak exercise and at ventilatory anaerobic threshold was 26.1 +/- 1.1 and 17.2 +/- 0.5 ml/min/kg, 25.4 +/- 1.1 and 16.9 +/- 0.8 ml/min/kg, and 26.4 +/- 1.3 and 17.5 +/- 1.2 ml/min/kg in normotensive subjects, those with mild hypertension, and those with moderate to severe hypertension, respectively. Fourteen normotensive subjects, six with mild hypertension, and nine with moderate to severe hypertension participated to step 2 (nifedipine vs placebo, double-blind crossover). Nifedipine reduced blood pressure at rest and at peak exercise in those with hypertension. Peak exercise VO2 was unaffected by nifedipine in both normotensive subjects and those with hypertension. With nifedipine, ventilatory anaerobic threshold occurred earlier and at a lower VO2 in mild and in moderate to severe hypertension (delta VO2 = -1.9 and -2.4 ml/min/kg, respectively). These findings might be due to nifedipine-induced redistribution of blood flow during exercise and might be the reason for the complaint of weakness after blood pressure reduction in hypertensive subjects.

[The right ventricle and pulmonary circulation in hypertensive patients]. / Il cuore destro e il circolo polmonare nell'iperteso.

Elevated blood pressure and vascular resistance in patients with systemic hypertension are paralleled by a proportional rise in pressure and resistance in the lesser circulation. It was hypothesized that increased systemic reaction to adrenergic stimulation is shared by the pulmonary vessels. Thus normotensive subjects and patients with primary hypertension were investigated during mental arithmetic and the cold pressor test. Both groups responded to both stimuli; during arithmetic pressure reaction was mediated through an increase of cardiac output, and during the cold pressor test through a predominant rise in systemic vascular resistance. The pressure changes were emphasized in the hypertensive population. Pressure in the pulmonary artery in normotensive subjects was not affected by cold and was slightly raised (systolic) during arithmetic. In hypertensive patients, on the other hand, systolic and diastolic pressures were consistently augmented by both tests, and pulmonary arteriolar resistance rose by 42% and 29% of control during the cold pressor test and arithmetic, respectively. Changes in resistance reflected neurally-mediated vasoconstriction but not variations in the passive relationship between pressure and flow, since during arithmetic, for a similar rise in flow the driving pressure across the lungs was steady in normotensive subjects and rose significantly in hypertensive patients. In these same patients pressure was augmented by cold test in the absence of substantial changes in flow. At baseline and during tests pulmonary wedge pressure, pleural pressure, arterial blood gases, and pH were similar in the two populations. The intravenous infusion of similar scalar doses of norepinephrine (the same mediator released during cold test) was not effective on the pulmonary vessels of normotensives and caused an obvious vasoconstriction in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

[Loculated pericardial effusion leading to functional tricuspid stenosis in a case of rheumatoid arthritis]. / Versamento pericardico loculato condizionante stenosi funzionale della tricuspide in un caso di artrite reumatoide.

We describe a case of loculated pericardial effusion, occurring in a women affected by rheumatoid arthritis. Because of its peculiar location, close to the atrioventricular plane, the effusion caused a haemodynamic pattern resembling tricuspid valve stenosis.

Hypersensitivity of lung vessels to catecholamines in systemic hypertension.

Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure.

Electrocardiographic alterations suggestive of myocardial injury elicited by rapid pressure lowering in hypertension.

In hypertensive cardiac hypertrophy, the elevated coronary perfusion pressure compensates importantly for the raised coronary resistance. An imbalance between perfusion and left ventricular (LV) mass, such as that occurring with rapid or excessive blood pressure lowering, may result in an inadequate oxygen supply. In 28 primary hypertensives (Group A) with LV mass index within the mean + 1 SD (96 + 19 g m-2) of 145 controls, and in 26 patients whose LV mass exceeded these values (Group B), we lowered the diastolic blood pressure rapidly to 85-90 mmHg, using both s.l. nifedipine and i.v. nitroprusside. During each test, eight patients in Group B had inversion of T waves in lead I, aVL, V3-V6, which waxed and waned in parallel with the pressure fall and recovery, and was independent of conduction disturbances, variations or group differences in the QRS axis, QTc interval, heart rate, LV fractional shortening and wall stress. A 'coronary steal phenomenon' or passive collapse in compliant lesions consequent to vasodilatation may trigger acute myocardial ischaemia in the presence of severe coronary disease. Patients developing the ECG alterations, however, were free from angina and four, who were subjected to coronary angiography, had normal arteriograms. Patients with the myocardial injury pattern showed greater LV mass indices and larger falls in diastolic pressure for it to reach normal levels. The supply of energy to the hypertrophied hypertensive heart seems to depend importantly on the coronary perfusion pressure, suggesting the cautious use of rapid acting drugs.

Enhanced hypoxic pulmonary vasoconstriction in hypertension.

In this study, we tested the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension. The hypothesis took origin from the following two considerations: alveolar hypoxia constricts the pulmonary vessels by enhancing the Ca2+ penetration across sarcolemma of the smooth muscle cells and systemic high blood pressure is associated with an elevation of tone and reactivity of the lung vessels, which seems to depend on an excessive cytosol free Ca2+ concentration due to alterations in sodium handling and in the Na+-Ca2+ exchange system. These considerations suggest the possibility that the disorders in the biochemistry of smooth muscle contraction in hypertension facilitate the rise of cytosol Ca2+ concentration during alveolar hypoxia, thus resulting in a potentiation of the vasoconstrictor properties of this stimulus. In 43 hypertensive and 17 normotensive men, pulmonary arteriolar resistance has been evaluated during air respiration and after 15 minutes of breathing 17%, 15%, and 12% oxygen in nitrogen. Curves relating changes in pulmonary arteriolar resistance to oxygen breathing contents had similar configuration in the two populations but in hypertension were steeper and significantly shifted to the left, reflecting a lower threshold and an enhanced reactivity. This pattern was not related to differences in severity of the hypoxic stimulus, plasma catecholamine concentration, or hypocapnia and respiratory alkalosis induced by hypoxia and probably was not mediated through alpha-receptor activation. Calcium channel blockade with nifedipine was able to almost abolish both the normotensive and the hypertensive pulmonary vasoconstriction reaction. These findings support the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension.

Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin.

BACKGROUND: KII ACE, the enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the lungs; its blockade reduces exposure to angiotensin II and enhances exposure to prostaglandins generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors improve pulmonary function in chronic heart failure (CHF) by readjusting lung vessel tone and permeability or alveolar-capillary membrane diffusion. METHODS AND RESULTS: In 16 CHF patients and 16 normal volunteers or mild untreated hypertensives, pulmonary function and exercise tests with respiratory gas analysis were assessed on placebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or aspirin, in random order and double blind, for 15 days each. In CHF, enalapril increased pulmonary carbon monoxide diffusion (DLCO), oxygen consumption (VO2), and exercise tolerance and reduced the ratio of dead space to tidal volume (VD/VT) and the ventilatory equivalent for carbon dioxide production (VE/VCO2). On enalapril, VO2 (r = .80, P < .0001) and VD/VT (r = -.69, P = .003) changes from placebo correlated with those in DLCO. These effects were inhibited by aspirin and were absent in control subjects. In 8 additional patients, hydralazine-isosorbide dinitrate, as an alternative treatment for reducing pulmonary capillary wedge pressure (PCWP) and increasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and VE/VCO2; amelioration in VO2 and VD/VT was unrelated to DLCO and was not modified by aspirin. CONCLUSIONS: ACE inhibition improved pulmonary diffusion in CHF. Hydralazine-isosorbide dinitrate failed to provide this result. Counteraction by aspirin, a prostaglandin inhibitor, bespeaks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar-capillary membrane diffusion.

[The antagonistic effect of aspirin on the expression of prostaglandin participation in the antihypertensive activity of ACE inhibitors]. / Effetto controattivo dell'aspirina quale espressione della partecipazione prostaglandinica all'attività antipertensiva dell'ACE-inibizione.

ACE-inhibitors antagonize both angiotensin production and bradykinin breakdown, resulting in enhancement of vasodilating prostaglandin release. This provides an explanation for the experimental observation that cycloxygenase blockers (such as aspirin or indomethacin) may counteract the antihypertensive efficacy of the ACE-inhibitors; it may be also possible that hypertensive patients taking aspirin as an antiplatelet agent may fail to benefit from ACE-inhibition. This study was aimed at: evaluating the magnitude and incidence of the inhibitory phenomenon; defining the minimal aspirin dosage that produces an antagonistic effect, as well as the possible reasons for a different individual susceptibility. We have studied untreated patients with mild (10 cases, Group 1), moderate (16 cases, Group 2) or severe (26 cases, Group 3) hypertension. The ACE-inhibitor enalapril was used at doses of 10 mg bid (groups 1 and 2) or 20 mg bid (Group 3). Active drug treatment periods had a 5-day duration. A daily dose of aspirin of 100 mg had no effect on the antihypertensive efficacy of enalapril. On the contrary, when a dose of 300 mg was used, 60, 57 and 50% of patients in Group 1, 2 and 3, respectively, showed a > 20% restraint of the mean arterial pressure fall with enalapril (20% was the lower arbitrary limit for defining antagonism). Inhibition was independent of the sequence of drug administration. In these patients counteraction averaged 60, 70 and 90%, respectively. In them, and not in the remaining patients in each group, aspirin substantially attenuated the renin rise elicited by ACE-inhibition. These data suggest that: a dosage of 100 mg aspirin is devoid of any inhibitory effect; more that 50% of ACE inhibited patients are, at least in the short term, susceptible to the action of 300 mg aspirin, regardless of the severity of hypertension; counteraction is seemingly mediated through a prostaglandin inhibition and depends on the individual predominance of prostaglandin activation (also as a renin secretory stimulus) or angiotensin inhibition by the ACE-inhibitor.

Rapid diagnosis and management of thoracic aortic dissection and intramural haematoma: a prospective study of advantages of multiplane vs. biplane transoesophageal echocardiography.

AIMS: The purposes of this study were to compare the accuracy of multiplane vs. biplane transoesophageal echocardiography (TEE) in the diagnosis of aortic dissection and aortic intramural haematoma, and to test whether these techniques provide all the diagnostic information required to make management decisions. METHODS AND RESULTS: Fifty-eight consecutive patients with clinically suspected aortic dissection were studied with multiplane TEE; all cases who required surgery underwent intraoperative monitoring with multiplane TEE. The following multiplane TEE data were analysed: the angle between current and 0 degrees plane at which each view was obtained; the success rate in the evaluation of true and false lumen, entry tear, coronary artery involvement, aortic regurgitation, pericardial effusion. Advantages of multiplane over biplane TEE have been evaluated by the demonstration of usefulness of views obtained in planes other than 0 degrees-20 degrees or 70 degrees-110 degrees, assuming that with manipulation of a biplane probe a 20 degrees arc could be added to the conventional horizontal and vertical planes. On the basis of TEE findings, aortic dissection was confirmed in 36 cases (18 type A, 12 type B, six intramural haematoma). The specificity and sensitivity of TEE in terms of the presence or absence of aortic dissection or intramural haematoma were 100%. An additional clinical value of multiplane over biplane TEE in the evaluation of ascending aorta, aortic arch, entry tears and coronary artery involvement was demonstrated. All cases with type A aortic dissection or intramural haematoma involving the ascending aorta had an operation that was performed immediately after the diagnosis (hospital mortality, 13%). Patients with type B aortic dissection were treated medically; 25% of these cases were operated later (hospital mortality, 0%). CONCLUSIONS: Multiplane and biplane TEE have excellent and similar accuracies in the evaluation of aortic dissection and intramural haematoma. Multiplane TEE improves the visualization of coronary arteries, aortic arch and entry tears; it appears to be an ideal method as the sole diagnostic approach before surgery in type A aortic dissection.

[The improvement of the Doppler echocardiographic method for the estimation of pulmonary systolic pressure]. / Perfezionamento del metodo ecocardiografico Doppler per il calcolo della pressione sistolica polmonare.

The formulas currently utilized for noninvasive evaluation of right ventricular systolic pressure (RVSP) include right ventricular-right atrial pressure gradient (RV-RAG) and right atrial pressure (RAP). The former is expressed by trans-tricuspid systolic flow velocity, the latter is generally assumed. We recently observed that ultrasound estimation of RAP through inferior vena cava collapsibility index (CI) may help in the choice of the more appropriate formula for the evaluation of RVSP. However, these traditional methods (method A:RV-RAG + 10; method B:RV-RAG x 1.1 + 14) have limitations, particularly when RAP is low. The present study was undertaken to improve noninvasive estimation of RVSP through new formulas based on CI prediction of RAP. One hundred and four patients, in whom tricuspid regurgitation was adequately documented with CW-Doppler, were included in this study. They were classified into 3 groups: Group 1 with CI > 45%, Group 2 with CI < or = 35%, Group 3 with CI 35-45%. RVSP was evaluated by 3 different methods: A, B, and C. Method C was based on CI, assigning 6, 16, or 9 mmHg to RAP (respectively, the mean values in the 3 groups of our previous study). Results indicate that method C improves noninvasive estimation of RVSP in Group 1 and Group 2, with respect to other methods, with reduction of the SEE and of the mean difference of the t-test between hemodynamic and echographic values. In Group 3, Doppler estimation by method A and C, and catheter measurements are comparable, whereas method B significantly overestimates the actual value.(ABSTRACT TRUNCATED AT 250 WORDS)

[Multiplane transesophageal echocardiography for the monitoring of cardiac surgery]. / L'ecocardiografia transesofagea multiplana per il monitoraggio di interventi di cardiochirurgia.

Multiplane transesophageal echocardiography (TEE) allows visualization of the heart and great vessels through an infinite number of imaging planes and improves the diagnostic capabilities of mono and biplane TEE. This study was undertaken to test whether MTEE is a useful intraoperative monitoring method during cardiac surgery. Intraoperative multiplane TEE was performed in 200 patients (mean age 56 +/- 19 years) as a part of the routine clinical care. We systematically acquired cardiac images from the gastric fundus (short and long axes of the ventricles), lower esophagus (four-chamber, two-chamber, and long axis), upper esophagus (13 views concerning the aorta, pulmonary artery, left and right atrium, systemic and pulmonary veins, coronary arteries, right ventricular outflow tract), and searched for complete views of the thoracic descending aorta. All views analyzed in the preoperative (immediately before cardiopulmonary bypass), intraoperative and postoperative phases evaluating: the angle between current and 0 degree at which each view was obtained; the success rate of each view; the usefulness of the different views in providing essential additional clinical information compared to 0 degrees and 90 degrees of the traditional biplane TEE. Most views of the heart and great vessels were visualized in oblique planes, and other views were significantly improved thanks to slight angle corrections. Multiplane TEE was particularly useful in the preoperative and postoperative phases of aortic dissection (11 cases), mitral valve repair (13 cases), left ventricular aneurysmectomy (9 cases), right atrial thrombosis (1 case), positioning of left ventricular hemopump (2 cases), mitral-aortic endocarditis (3 cases), bleeding from proximal suture of an aortic heterograft (1 case).(ABSTRACT TRUNCATED AT 250 WORDS)