Pedro Forcada

Reduction of reperfusion injury with preoperative rapid intravenous infusion of taurine during myocardial revascularization

To assess a possible free-radical scavenging action of taurine during coronary artery bypass grafting, 12 patients were randomly divided into two equal groups. One to 3 hours before surgery, they received a rapid intravenous infusion of either placebo (group 1) or taurine (5 gm) (group 2). During surgery, biopsy samples were taken before ischemia (preischemic samples) and after 10 minutes of reperfusion (reperfusion samples). Lipoperoxidation was determined by hydroperoxide-initiated chemiluminescence of heart homogenates, and myocardial cell damage was assessed by electron microscopy. The values for chemiluminescence in preischemic and reperfusion samples from group 1 were 7500 +/- 1600 and 18,600 +/- 4600 cpm/mg of protein, respectively (p less than 0.03). This difference was not observed in group 2 where the values were 10,050 +/- 2700 and 11,800 +/- 4200 cpm/mg of protein, for preischemic and reperfusion samples, respectively. The number of severely damaged mitochondria (grades 3 and 4) in reperfusion samples from group 1 increased significantly compared to preischemic samples (25 +/- 8% vs 12 +/- 3%, p less than 0.01). Conversely no differences were observed between the number of severely damaged mitochondria in reperfusion and preischemic samples from group 2 (8 +/- 3% vs 8 +/- 2%). The number of damaged and necrotic myocytes increased in group 1 after reperfusion from 22 +/- 9% to 34 +/- 10% (p less than 0.03) and from 10 +/- 7% to 26 +/- 20% (p = NS), respectively. No changes were observed between reperfusion and preischemic samples in group 2. Treatment with taurine seems to reduce lipoperoxidation and decrease cell damage at the time of reperfusion.

Inapparent myocarditis and sudden death in pediatrics. Diagnosis by immunohistochemical staining

We analyzed the anatomopathological findings in two cases of sudden death related to myocarditis in pediatric patients. Since the diagnosis of myocarditis depends either upon histologic and histochemical techniques or the manner the sample was obtained, we describe a more specific immunohistochemical method to stain samples and more accurately diagnose and qualify cellular lymphoid strains in the inflammatory reaction of the myocardium thus allowing a correct diagnosis of myocarditis.

Sodium Intake Is Associated With Parasympathetic Tone and Metabolic Parameters in Mild Hypertension

BACKGROUND Although the impairment of parasympathetic cardiac control was described in hypertensives submitted to a high salt diet, the impact of this autonomic abnormality on metabolic and inflammation markers in patients with mild hypertension has not been explored. METHODS Four hundred and ninety mild essential hypertensive patients (144 ± 9/94 ± 9 mm Hg, 49.5 ± 13.9 years, 67.9 % male) were studied. Dietary sodium intake was estimated by measuring 24-h urinary sodium excretion (UNa), and the patients were classified according to UNa levels as follows: low (<50 mEq/l), medium (50-99 mEq/l), and high UNa (≥100 mEq/l). Parasympathetic tone was evaluated by assessing heart rate recovery (HRR) after an exercise stress test. HRR, plasma lipids, glucose metabolism, and inflammatory biomarkers were compared across UNa groups. RESULTS HRR and high-density lipoprotein (HDL)-cholesterol were progressively lower, and insulin (INS), homeostasis model assessment of insulin resistance (HOMAir), ultrasensitive-C-reactive protein (usCRP) were progressively higher across increasing UNa groups. In the low and medium UNa groups, HDL-cholesterol was higher and CRP was lower than that in high UNa (P < 0.01 and P < 0.05, respectively) (Dunnett post-hoc test). In the low UNa group, triglycerides (TGs), INS, and HOMAir were lower than that in high UNa (P < 0.05). Multiple linear regression analysis showed that UNa, HOMAir, and heart rate (HR) were negatively associated with HRR (P < 0.0001, P < 0.0001, and P = 0.001, respectively). CONCLUSIONS In the essential hypertensive patients studied high sodium intake is associated with parasympathetic inhibition, lipid disturbances, and inflammation. Studies designed to assess causality between sodium intake and metabolic and autonomic status are needed to evaluate the relevance of controlling sodium intake, especially in hypertensive patients.

Psychosocial Stress and Low Resilience: a Risk Factor for Hypertension

Full Member of Sociedad Argentina de Cardiología Winning work of the Braun Menéndez Prize – Clinical Cardiology – at the XXXV Argentine Congress of Cardiology CEDIE Center for Endocrinology Researches, Hospital de Niños. Clínica Privada del Carmen. Zárate, Province of Buenos Aires 1 Cardiology Consultant 2 CONICET Researcher 3 Chief of Non-Invasive Laboratory of the Hospital Universitario Austral 4 Cardiologist 5 Biochemist. Chief of Laboratory Background Chronic psychosocial stress (CPS) was proposed as a cardiovascular risk factor (CRF); however, the complexity and the lack of objective measures to evaluate it, together with the fact that not all individuals react in the same way, determined the lack of conclusive studies.

Are plasma renin activity and aldosterone levels useful as a screening test to differentiate between unilateral and bilateral renal artery stenosis in hypertensive patients

Objective To evaluate the serum aldosterone (Ald)/plasmatic renin activity (PRA) ratio as a surrogate marker of renin–angiotensin–aldosterone system status in unilateral (Uni)- and bilateral (Bi)-renal artery stenosis (RAS). Methods Seven hundred and eight hypertensive patients (HTP) were studied. Intermediate and high pretest risk of RAS was detected in 66 HTP who subsequently underwent renal gadolinium-enhanced magnetic resonance and arteriography. After application of exclusion criteria 51 HTP remained: 16 with Uni-RAS, 16 with Bi-RAS and 19 essential hypertensives with normal arteries. Nineteen normotensive individuals were also studied. Ald and PRA were determined before and after stenosis resolution by balloon angioplasty and stent implantation. Results Ald/PRA (ng/dl per (ng/ml per h−1)) was markedly high in Bi-RAS (5.92 ± 2.30, P < 0.001), and markedly low in Uni-RAS (0.38 ± 0.17, P < 0.001) versus essential hypertensives (1.52 ± 2.02). Multilevel likelihood ratios for Bi-RAS were positive for Ald/PRA higher than 3.6, negative for Ald/PRA lower than 0.2, and neutral for Ald/PRA at least 0.2 and 3.6 or less. ROC analysis identified Ald/PRA lower than 0.5 and Ald/PRA higher than 3.7 to have the best sensitivity and specificity to detect Uni-RAS and Bi-RAS, respectively. In Uni-RAS, but not in Bi-RAS, postinterventional PRA was significantly lower than basal PRA. In Uni-RAS and Bi-RAS, postinterventional Ald was approximately 30% and approximately three times lower than basal Ald, respectively. In essential hypertensives, PRA and Ald showed no changes in the same period. Conclusion In the population studied, Ald, PRA and Ald/PRA were significantly different among essential hypertensives, and HTP with Uni-RAS or Bi-RAS. Studies with a higher number of patients will allow exploration of the usefulness of pharmacologic aldosterone blockade in Bi-RAS, and to assess the relevance of Ald/PRA to differentiate Uni-RAS from Bi-RAS.

Mitochondrial oxidative and structural damage in ischemia-reperfusion in human myocardium. Current knowledge and future directions.

The sequence of events in heart ischemia-reperfusion has been clearly documented in experimental animal models but not in cardiac surgery patients. The evidence in human studies had not been gathered in a systematic and comprehensive fashion, so as to provide an encompassing picture of the phenomenon. This limits our ability to devise appropriate strategies for optimal perioperative myocardial protection. We present here a review or our experience in myocardial ischemia-reperfusion in a historical perspective. From our previous studies we conclude that, although several issues still remain unsolved, there is no doubt that oxygen-free radicals are important contributors to myocardial injury during the reperfusion period of coronary artery bypass surgery. Yet, in spite of this wealth of information, both clinical and experimental, subsequent clinical trials conducted over the last several years with a variety of antioxidant strategies have been largely disappointing. Therefore, the whole paradigm of oxidative stress in cardiac injury needs to be re-evaluated. In this regard, differences between past and current knowledge are discussed, and future directions are traced. We concluded that patients subjected to elective bypass surgery undergo oxidative stress upon reperfusion after cardioplegic arrest; the magnitude of the phenomenon, however, is at present small and may not justify widespread antioxidant therapy.

The hypertrophied myocardium and coronary disease. Structural changes in patients submitted to aortocoronary bypass surgery

Seventeen patients with coronary disease submitted to myocardial revascularization were studied. Ten patients had a hypertrophied ventricle, and 7 had normal ventricular mass. Myocardial biopsies were obtained before ischemia and at the time of reperfusion and were assessed for: volume fraction of fibrous tissue, myocyte diameter, morphometric mitochondrial studies and ultrastructural changes. The volume fraction of fibrous tissue in patients with hypertrophied ventricle was 1.9 +/- 0.04, and in patients with normal ventricular mass was 0.9 +/- 0.01 (p less than 0.05). The diameter of the myocyte was 23 +/- 0.3 microns and 18 +/- 1.2 microns for patients with hypertrophied and normal ventricular mass, respectively (p less than 0.01). The value of volumetric density for pre-ischemia samples in patients with a hypertrophied ventricle was 23 +/- 2.2 and in patients with normal ventricular mass was 35 +/- 2.7 (p less than 0.02). Grades 3 and 4 of damaged mitochondria were significantly increased in reperfusion samples from patients with a hypertrophied ventricle compared to pre-ischemia samples. Collagen growth was increased in hypertrophied hearts which were also more sensitive to the ischemia/reperfusion mechanism.

Lack of RAAS inhibition by high-salt intake is associated with arterial stiffness in hypertensive patients

Hypothesis/introduction: The relationship between salt intake, blood pressure and RAAS activation is still controversial, being that both high- and low-salt intakes are associated with cardiovascular events in a J-shaped curve pattern. We hypothesized that different patterns of RAAS response to dietary salt intake among hypertensives could be identified, while vascular damage would be related to high-salt intake plus absence of expected RAAS inhibition. Objective: We aim to assess the relationship between sodium intake, RAAS and vascular stiffness in hypertension. Materials and methods: We screened 681 hypertensive patients for urinary/plasma electrolytes, renin, aldosterone and pulse wave velocity (PWV) under their usual salt intake level. Results: After applying exclusion criteria, an inverse relation between urinary sodium and RAAS was observed in the 300 remaining subjects. Additionally, four types of response were identified: 1) Low (L) sodium (S)-Low RAAS, 2) LS-High (H) SRAAS, 3) HS-Low RAAS, 4) HS-High RAAS. We found no differences in age/BP among groups, but type 4 response individuals included more females and a higher pulse wave velocity. Conclusions: We showed a) an inverse salt-RAAS relation, b) an association between HS plus high RAAS with increased PWV that could identify a higher-risk hypertensive condition.

DEPRESSION-MEDIATED ARTERIAL STIFFNESS AND AUTONOMIC DISBALANCE IN YOUNG HYPERTENSIVE PATIENTS: A PATHWAY TO STROKE?: PP.4.144

Systemic hypertension and depression are currently considered risk factors for cardio-cerebral-vascular disease and particularly for stroke. The mechanisms how depression increases the risk of stroke have not been fully elucidated. It is also well known that elevated pulse wave velocity (PWV) as evidence of arterial stiffness and target organ damage (TOD) increases risk of cerebral events. Furthermore, autonomic disbalance has been related as a physiopatological mechanism in depression and cardiovascular disease. Based on this unexplored issue, we explored the hyphotesis that the association between hypertension and depression is related to greater PWV increase, and that autonomic disbalance could be one of the pathways involved. Objective: To evaluate PWV and the autonomic balance in young hipertensive patients with depression. Methods: We studied 34 consecutive hypertensive patients (39 ± 9,1 years; 68 % men) admitted for TOD assessment. All patients completed voluntarily a sheet with two questions validated for depression screening and validated scales (CES-D/Hamilton) to obtain a severity score of depression. Arterial stiffness was determined by non-invasive PWV measurement and autonomic response by heart rate variability, previously described by others, during stress test recovery period. Results: This population was analyzed in a 2:1 ratio, classified as depressive (n:11) when at least one question was positive, and non-depressive (n:23) when both were negative. Results were analyzed with chi2 and T-test. There were no significative differences in baseline characteristics. Depressive patients showed a significative higher PWV (11 ± 2,1 vs 9,2 ± 1,6 m/s; p = 0.025). There was also found a difference in stress test recovery period, showing a faster recovery in the same group (p = 0.006). Figure 1. No caption available. Conclusions: An association between an increased arterial stiffness, autonomic disbalance and depression was found in the young hypertensive population we evaluated. Further studies would be necessary to identify their contribution to the increased risk of stroke previously reported (MRFIT/WHI). Autonomic disbalance could be a probable physiopathological pathway while arterial stiffness would be a marker of its early atherosclerotic impact.

EFFECTS OF VENTRICULAR GEOMETRY ON VENTRICULAR ARTERIAL COUPLING IN ESSENTIAL HYPERTENSION: PP.8.341

Introduction: Echocardiography is used to assess ventrículo-arterial coupling (VAC) determined by the balance between the contractile properties of left ventricle (LV) and the pressure load. However ventricular geometry (VG) and cardiac hypertrophy (LVH) may modulate the VAC in hypertension (HT). Adaptative variations of aortic (Eal) and ventricular (Ees) elastances may be related with VAC changes within normal systolic function (SF). Objective: To characterize non-invasively the interaction between VG and VAC in HT within normal range of SF and VAC. Methods: We evaluated 23 consecutives hypertensive patients, age 53,3 ± 9,8, male 12(52,2%) female 11 (47,8%), SBP 134,78 ± 12,8 mmHg, DBP 82,47 ± 8,21 mmHg, with Doppler Echocardiography (Vivid 7,GE), using simple pulse method modified for the calculation of Ees and the ratio of end systolic pressure to stroke volume for Eal. VAC is the ratio Eal/Ees.Elastances were normalized to 100 g of ventricular mass. The following measurements were also determined: Mesoparietal fractional shortening, normalized systolic stress (MFS/STRESS), left atrial diameter (LA), correlation E/A (E/A), diastolic isovolumic relaxation time (Tau), systolic work index (SWI), systolic volume index (SVI) and peripheral vascular resistance index (PVRI). The VG was classified as: normal (Nor), concentric remodeling (Rem), concentric LVH (Conc) and eccentric LVH (Exc). Results: Significative differences on the VG were found in Nor with Rem: Ees(p < 0,05); Conc: LA(p < 0,01), Eal(p < 0,01), E/A(p < 0,01), SWI(p < 0,05); Exc: SWI(p < 0,05), SVI(p < 0,05), LA(p < 0,05), Eal(p < 0,01). Conclusions: In HT with SF and VAC within normal ranges, VG seems to affect VAC, contractility and ventricular performance. The noninvasive measurement of VG and related VAC, may be useful for diagnostic and therapeutic porpoises in early stages in hypertensive patients. Figure 1. No caption available.