Regression Of Structural Changes Research Articles

Reversible Apical Hypertrophy in a Young Competitive Athlete with Familiar Hypertrophic Cardiomyopathy.

BACKGROUND Differential diagnosis between athlete's heart and hypertrophic cardiomyopathy is sometimes challenging in sport cardiology since endurance training can cause a distinct pattern of functional and structural changes of the cardiovascular system. It is of crucial importance to accurately diagnose it and stratify the arrhythmic risk since hypertrophic cardiomyopathy is one of the leading causes of sudden cardiac death in young athletes. Apical hypertrophic cardiomyopathy is a relatively rare form of hypertrophic cardiomyopathy that predominantly affects the apex of the left ventricle and usually has a nonobstructive physiology. Few data and studies are available on influence of aerobic training (and detraining) on morphological changes in athletes with apical hypertrophic cardiomyopathy. CASE REPORT We present the case of a 19-year-old male soccer athlete with family history for obstructive hypertrophic cardiomyopathy, with electrocardiographic and morphological left ventricular remodeling in association with sports activity. Intensive aerobic training led to marked T-wave inversion on 12-lead ECG and left ventricular hypertrophy compatible with apical hypertrophic cardiomyopathy. Genetic testing confirmed the presence of familial variant c853C>T, p.(Arg 285Cys) on TNNT2 gene. After 18 months detraining, we observed a complete regression of ECG abnormalities and a reverse remodeling of the left ventricular hypertrophy. No pharmacological therapy was indicated; periodic cardiological evaluations were advised. Monitoring devices or implantable cardioverter defibrillator were not recommended. CONCLUSIONS This case suggests that intensive aerobic training can affect the pathological hypertrophic cardiomyopathy substrate, facilitating the development of left ventricular hypertrophy and, more interesting, regression of structural changes after detraining.

IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma.

Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

Effects of blood pressure lowering with amlodipine or lisinopril on vascular structure of the common carotid artery

Increased intima-media thickness of the common carotid artery predicts increased risk of myocardial infarction and stroke. Preliminary evidence suggests that a decrease in blood pressure (BP) is associated with diminished wall thickness. It is not known if all classes of anti-hypertensive agents have similar protective effects. In this double-blind parallel-group clinical trial, 69 previously untreated patients with hypertension were allocated randomly to 1 year of treatment with either amlodipine (5-10 mg daily) or lisinopril (5-20 mg daily). Doxazosin and bendrofluazide were added if required to achieve BP control. After 12 months of treatment, clinic BP, ambulatory BP and cardiac mass were reduced similarly by the two treatment regimens. Common carotid artery intima-media thickness decreased by 0.048 mm (95% confidence intervals -0.066, -0.031 mm) in the amlodipine-treated group, but decreased by only 0.027 mm (-0.046, -0.007 mm) in the lisinopril-treated group (P<0.05 for difference between treatments). Common carotid artery lumen diameter declined significantly only in patients treated with lisinopril [amlodipine, -0.02 mm (-0.14, 0.10 mm); lisinopril, -0.21 mm (-0.32, -0.11 mm); P<0.02], while intima-media area declined similarly in the two treatment groups [amlodipine -1.32 mm(2) (-1.91, -0.74 mm(2)), lisinopril -1.26 mm(2) (-1.80, -0.72 mm(2)); not significant]. The results confirm that a decrease in BP causes regression of structural changes in the carotid artery in hypertensive patients. The nature of the structural regression differed markedly between the two treatment regimens, in spite of similar decreases in BP. The calcium channel blocker induced greater regression of common carotid artery intima-media thickness than the angiotensin-converting enzyme inhibitor. However, carotid artery wall mass, as indicated by intima-media area, was reduced to a similar extent by the two treatments. It remains to be established whether such differences confer a prognostic advantage.

Arterial hypertension: its impact on perioperative morbidity and mortality

Chronic hypertension is associated with structural as well as functional changes of the vasculature, in particular of the coronary, cerebral and renal circulation. It is important to realise that [1] functional changes are often the result of structural changes, [2] the longer lasting the hypertension, the slower and less complete the regression of structural changes, and [3] acute "normalisation" of arterial pressure in long-standing hypertension may initially induce functionally subnormal smooth muscle and/or cardiac activity because the structure of the cardiovascular system is adapted to function at elevated pressures. Despite a multitude of studies, the impact of hypertension on peri-operative morbidity and mortality remains controversial. There are as many studies seeming to suggest that preoperative hypertension correlates with adverse outcome as there are studies that fail to establish such a relationship. When looking at the combined evidence, one is inclined to conclude that hypertension is a predictor of "soft" outcomes (e.g. peri-operative myocardial ischaemia and transient post-operative neurologic deficit) rather than an independent predictor of "hard" outcomes (e.g. unstable angina, myocardial infarction and cardiac death). In view of lack of convincing outcome data, it is impossible to recommend a generally acceptable management strategy for the hypertensive patient. Although, in general, a gradual reduction of blood pressure over a period of weeks to months is the optimal therapeutic approach, we will be hard-pressed delaying surgery for the sole purpose of "better blood pressure control". With full appreciation and detailed knowledge of the pathophysiology of hypertension, combined with sophisticated haemodynamic monitoring and interventions in the peri-operative period, acutely anaesthetising an inadequately treated hypertensive patient will probably not adversely affect his outcome. Delaying surgery for additional work-up may possibly improve outcome in patients with target organ disease, evidence of secondary hypertension, in the most severe forms of hypertension or sudden-onset hypertension.

Impact of systemic hypertension on peri-operative morbidity and mortality

Chronic hypertension is associated with structural as well as functional changes of the vasculature, in particular of the coronary, cerebral and renal circulations. It is important to realize that (1) functional changes are often the result of structural changes, (2) the longer lasting the hypertension, the slower and less complete the regression of structural changes, and (3) acute ‘normalization' of arterial pressure in longstanding hypertension may initially induce functionally subnormal smooth muscle and/or cardiac activity because the structure of the cardiovascular system is adapted to function at elevated pressures. Despite a multitude of studies, the impact of hypertension on peri-operative morbidity and mortality remains controversal. There are as many studies seeming to suggest that pre-operative hypertension correlates with adverse outcome as there are studies that fail to establish such a relationship. When looking at the combined evidence, one is inclined to conclude that hypertension is a predictor of ‘soft' outcomes (e.g. peri-operative myocardial ischaemia and transient post-operative neurologic deficit) rather than an independent predictor of hard outcomes (e.g. unstable angina, myocardial infarction and cardiac death). In view of a lack of convincing outcome data, it is impossible to recommend a generally acceptable management strategy for the hypertensive patient. Although, in general, a gradual reduction of blood pressure over a period of weeks to months is the optimal therapeutic approach, we will be hard-pressed delaying surgery for the sole purpose of ‘better blood pressure control'. With full appreciation and detailed knowledge of the pathophysiology of hypertension, combined with sophisticated haemodynamic monitoring and interventions in the peri-operative period, acutely anaesthetizing an inadequately treated hypertensive patient will probably not adversely affect his outcome. Delaying surgery for additional work-up may possibly improve outcome in patients with target organ disease, evidence of secondary hypertension, in the most severe forms of hypertension or sudden-onset hypertension.

Inhibition of angiotensin II and platelet-derived growth factor-induced vascular smooth muscle cell proliferation by calcium entry blockers.

Structural changes within the blood vessel wall such as hyperplasia and hypertrophy of vascular smooth muscle cells are important factors in the pathogenesis of hypertension. Humoral growth factors such as angiotensin II (AII) and platelet-derived growth factor BB (PDGF-BB) may participate in the remodelling of the blood vessel wall. Whether and by which mechanisms antihypertensive treatment is capable of influencing the structural blood vessel alterations to date remains unclear. In the present study, the effect of nifedipine and diltiazem on AII- and PDGF-BB-induced vascular smooth muscle cell proliferation was examined. Nifedipine and diltiazem at a concentration of 10 microM did not affect baseline DNA synthesis in isolated vascular smooth muscle cells in culture. AII (final concentration 100 nM) and PDGF-BB (50 ng/ml) stimulated DNA synthesis by approximately 9.0- and 4.6-fold, respectively. Both AII- and PDGF-BB-induced DNA synthesis was significantly blunted by diltiazem and nifedipine in a concentration of 10 microM, while no significant influence was seen with concentrations from 10 nM up to 1 microM. In contrast, no significant influence of these drugs could be observed on fetal calf serum 5%-induced DNA synthesis. The findings indicate that calcium antagonists possess antimitogenic potential and that they may thus contribute to the regression of structural changes of the blood vessels associated with hypertension.

Regression of Cardiovascular Structural Changes—A Preventive Strategy

Left ventricular hypertrophy is an independent "risk factor" for all kinds of cardiovascular disease. Structural vascular changes are of importance for the maintenance and progression of high blood pressure. To try to achieve regression of these structural changes seems a logical option as part of a preventive strategy in hypertension. The effect of antihypertensive therapy on structural cardiovascular changes in animal models and man is reviewed. A prolonged normalization of blood pressure without reflexogenic activation of trophic factors, if possible started early in the development of hypertension seems to be the optimal therapy to attain regression. There are some data indicating that regression of cardiac hypertrophy can improve cardiac function and reduce arrhythmias and furthermore that regression of structural vascular changes can positively affect the progression of hypertension. Although these preliminary result look promising there are still no data on how regression induced by antihypertensive therapy affects the mortality and morbidity associated with left ventricular hypertrophy.

Specific Phosphodiesterase Inhibition and Maximal and Submaximal Exercise Performance in Patients with Congestive Heart Failure

The current therapeutic interest in specific phosphodiesterase (PDE) inhibition involves patients with severe congestive heart failure (CHF) whose symptoms are not controlled by diuretics, nitrates, angiotensin converting enzyme (ACE) inhibitors, and digitalis. Maximal exercise capacity is limited in these patients by an inadequate rise in cardiac output and a fixed capacity to dilate the skeletal muscle vasculature, which is perhaps compounded by disorders of the skeletal muscle metabolism. To improve maximal exercise capacity, the increase in cardiac performance produced by specific phosphodiesterase inhibitors must, in turn, reverse the abnormalities present in the periphery, and more specifically augment the capacity to dilate the skeletal muscle vasculature. Increased vasodilatory response to maximal exercise probably depends on the regression of structural changes in the skeletal muscle vasculature. Such regression may be mediated by a reduction in neurohormonal vasoconstrictor stimuli and/or chronic augmentation in resting limb blood flow. Submaximal exercise capacity, at work loads equivalent to less than 70% of peak aerobic capacity, appears to be directly limited by depressed cardiac output and high sympathetic vasoconstrictor activity. Specific phosphodiesterase inhibition, which consistently increases left ventricular performance during exercise, is more likely to improve exercise capacity at submaximal work loads than at maximal work loads.

Specific Phosphodiesterase Inhibition and Maximal and Submaximal Exercise Performance in Patients with Congestive Heart Failure

The current therapeutic interest in specific phosphodiesterase (PDE) inhibition involves patients with severe congestive heart failure (CHF) whose symptoms are not controlled by diuretics, nitrates, angiotensin converting enzyme (ACE) inhibitors, and digitalis. Maximal exercise capacity is limited in these patients by an inadequate rise in cardiac output and a fixed capacity to dilate the skeletal μscle vasculature, which is perhaps compounded by disorders of the skeletal μscle metabolism. To improve maximal exercise capacity, the increase in cardiac performance produced by specific phosphodiesterase inhibitors μst, in turn, reverse the abnormalities present in the periphery. and more specifically augment the capacity to dilate the skeletal μscle vasculature. Increased vasodilatory response to maximal exercise probably depends on the regression of structural changes in the skeletal μscle vasculature. Such regression may be mediated by a reduction in neurohormonal vasoconstrictor stiμli and/or chronic augmentation in resting limb blood flow. Submaximal exercise capacity, at work loads equivalent to less than 70% of peak aerobic capacity, appears to be directly limited by depressed cardiac output and high sympathetic vasoconstrictor activity. Specific phosphodiesterase inhibition. which consistently increases left ventricular performance during exercise, is more likely to improve exercise capacity at submaximal work loads than at maximal work loads

Hemodynamic Effects of β-Blocking Compounds Possessing Vasodilating Activity

The cardinal hemodynamic disturbance in established essential hypertension is an increased total peripheral resistance. Monotherapy with conventional beta-blockers lowers blood pressure usually without any significant fall in total peripheral resistance. Generally, cardiac output is reduced at rest as well as during exercise. In recent years, beta-blockers with vasodilating activity have been developed. Labetalol induces nonselective beta-blockade and in addition reduction in vascular resistance mainly through alpha-blockade. Long-term hemodynamic data indicate gradual normalization of cardiac output, stroke volume, and total peripheral resistance--possibly due to regression of structural changes in the left ventricle and in the arterioles. Prizidilol is a nonselective beta-blocker with a direct vasodilator effect. One year results showed a very marked fall in blood pressure and total peripheral resistance and dramatic increase in posttreatment exercise stroke volume. Cardiac output was unchanged in spite of a reduction in heart rate. Due to side effects, the drug has been withdrawn. Dilevalol, which is the R-R' isomer of labetalol, is also a nonselective beta-blocker, but its vasodilating activity seems to be mainly due to partial beta 2-agonist activity. Preliminary data indicate a reduction in blood pressure--mainly due to a fall in total peripheral resistance. Studies in elderly patients or in patients with reduced left ventricular function seem to indicate that the drug might be used without deterioration of the heart pump function. Although antihypertensive properties of dilevalol have been extensively studied and are defined, the exact position of dilevalol among antihypertensive drugs will be more precisely determined in future studies.

Regression of structural cardiovascular changes by antihypertensive therapy.

Structural vascular changes, consisting mainly of smooth muscle cell hypertrophy of the arterioles, have been found in various hypertensive animal models as well as in hypertensive patients. Although such changes may be to some extent a primary phenomenon in primary or essential hypertension, there is ample proof that an elevation in arterial pressure over a period of time will cause hyperplasia of the media in the resistance vessels; thus, this change is secondary to the rise in pressure. Studies in various animal models have shown that such structural arteriolar changes are reversible if a long-term reduction in arterial pressure can be obtained. In hypertensive patients reversibility of such changes has been demonstrated in some vascular beds as a result of chronic antihypertensive therapy. However, no complete "normalization" has ever been shown, probably because of inadequate reduction of arterial pressure and perhaps also because long-standing hypertension induces fibrosis of the arteriolar media, which is less likely to be positively affected by a lowering of blood pressure. In humans, some vascular beds, for example, the muscle vessel bed of the calves, appear to be less suitable for the demonstration of regression of structural changes. This could be due to erect posture, which increases the transmural pressure in these vessels, since the effect of gravity is added to the intravascular pressure. Finally, it is conceivable that effects other than the reduction in arterial pressure could play a role. Thus, antihypertensive drugs with a vasodilating action appear to be more effective in reducing structural vascular changes than drugs that do not have a vasodilating effect, even if an identical degree of blood pressure reduction is obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Short- and long-term (six-year) hemodynamic effects of labetalol in essential hypertension

The acute blood pressure lowering effect of intravenous labetalol (0.2 to 0.8 mg/kg) was studied in 11 patients with severe hypertension. The blood pressure was reduced by 22 percent partly due to a decrease in total peripheral resistance (−14 percent) and partly due to a reduction in cardiac output (−10 percent). Stroke volume was unchanged. Fifteen patients with moderate essential hypertension were studied at rest and during exercise before and after one and six years of labetalol therapy. Blood pressure was reduced approximately 22 percent at rest as well as during exercise, mainly due to a reduction in total peripheral resistance. However, after one year, cardiac index was reduced 10 to 14 percent (p < 0.01) at rest (sitting) and during exercise due to a reduction in heart rate not compensated for by an increase in stroke volume. During the next five years, blood pressure control was maintained, but cardiac index tended to increase and was not significantly reduced in any situation six years after treatment was started. Total peripheral resistance decreased significantly and was reduced 15 to 20 percent (p < 0.01) after six years. Stroke index increased about 10 to 15 percent (p <0.01). These alterations are the opposite of what is seen in untreated hypertensive patients restudied after 10 and 17 years. The normalization of central hemodynamics could reflect the regression of structural changes in the heart and in the resistance vessels.

Haemodynamic effects of withdrawal of long-term treatment with beta-adrenoceptor blocking agents in subjects with essential hypertension.

1. After 10 years of beta-adrenoceptor blockade in five female patients with essential hypertension, the beta-adrenoceptor-blocking agent was withdrawn, and the women were then followed up for 1 year, with measurements of cardiac output and peripheral resistance. 2. Blood pressure remained low during the first year after withdrawal in spite of the fact that the heart rate increased within the first few days. 3. Cardiac output was found to increase during the first year after withdrawal, although total peripheral resistance was essentially unchanged. 4. The maintenance of low blood pressure after withdrawal of the antihypertensive drug might indicate a regression of structural changes in the resistance vessels during successful long-term antihypertensive treatment. 5. Minimal resistance in hands and calves did not increase during the year after withdrawal.