Normal Myocardial Contractility Research Articles

Subacute and chronic post-COVID myocarditis: diagnostics, clinical variants, treatment approaches

Aim. To study the mechanisms and clinical variants of subacute and chronic myocarditis after SARS-CoV-2 infection using morphological and virological studies and to develop approaches to its treatment.Material and methods. The study included 89 patients with documented coronavirus disease 2019 (COVID-19). The diagnosis of post-COVID myocarditis was established based on myocardial biopsy and/or cardiac magnetic resonance imaging (MRI) data in combination with anamnesis, increased titers of anticardiac antibodies, and other criteria. The average time of presentation after infection was 8,0 [4; 17,5] months, while the average follow-up period was 7,0 [6,0; 13,5] months. Electrocardiography, Holter monitoring, echocardiography, cardiac MRI (n=60), determination of anticardiac antibody levels, myocardial biopsy (n=38), and autopsy (n=1) were performed.Results. All patients showed an association between the onset or exacerbation of cardiac symptoms and COVID-19. The clinical variants of post-COVID myocarditis were identified: arrhythmic (n=24) with newly developed arrhythmias with normal myocardial contractility; decompensated (n=65) with newly diagnosed heart failure, including a variant developed with primary (genetic) cardiomyopathies and amyloidosis (n=10). The profile of arrhythmias in the arrhythmic variant varied from potentially life-threatening rhythm and conduction disorders (sustained ventricular tachycardia, grade II-III atrioventricular block) to infrequent supraventricular premature beats. In the decompensated variant, lymphocytic myocarditis was most often morphologically detected, while eosinophilic and giant cell myocarditis, associated with a worse prognosis, were rarer. Simultaneous development of nonbacterial thrombotic endocarditis, infective endocarditis with the development of valvular heart defects was noted. In 10 cases, myocarditis was combined with primary cardiomyopathies, AL amyloidosis. Treatment included the administration of antiarrhythmic, cardiotropic, immunosuppressive therapy (glucocorticoids 16-32 mg/day in 68,5% of patients, hydroxychloroquine 200-400 mg/day in 33,7%). In the arrhythmic type, complete arrhythmia suppression was achieved in 25% of cases, while partial in 58,3%. In one case, a pacemaker was implanted. In patients with a decompensated myocarditis, corticosteroids were effective regardless of the viral genome/proteins in the myocardium.Conclusion. COVID-19 can induce subacute and chronic myocarditis with the development of isolated arrhythmias or severe heart failure.

Echocardiographic strain imaging in the pediatric heart: clinical value and utility in decision making.

Speckle tracking echocardiography (STE)-derived measures of myocardial mechanics, referred to herewithin as strain measurements, directly assess myocardial contractility and provide a nuanced assessment of ventricular function. This review provides an overview of strain measurements and their current clinical value and utility in decision making in pediatric cardiology. Strain measurements are advancing understanding of how cardiac dysfunction occurs in children with acquired and congenital heart disease (CHD). Global strain measurements can detect early changes in cardiac function and are reliable methods of serially monitoring systolic function in children. Global strain measurements are increasingly reported in echocardiographic assessment of ventricular function alongside ejection fraction. Research is increasingly focused on how strain measurements can help improve clinical management, risk stratification, and prognostic insight. Although more research is needed, preliminary studies provide hope that there will be clinical benefit for strain in pediatric cardiology management. Strain measurements provide a more detailed assessment of ventricular function than conventional measures of echocardiographic functional assessment. Strain measurements are increasingly being used to advance understanding of normal and abnormal myocardial contractility, to increase sensitivity to detect early cardiac dysfunction, and to improve prognostic management in children with acquired and CHD.

ХИРУРГИЧЕСКОЕ ЛЕЧЕНИЕ БОЛЬНЫХ ИБС СО СНИЖЕННОЙ СОКРАТИТЕЛЬНОЙ СПОСОБНОСТЬЮ МИОКАРДА ЛЕВОГО ЖЕЛУДОЧКА

The increased worldwide interest in performing coronary artery bypass grafting operations on a beating heart has made the question of the results of these operations in patients with low contractility of the left ventricular myocardium belonging to the high-risk category urgent. The aim of our study was a comparative assessment of the immediate results of surgical treatment of patients with reduced (LVEF <45%) and normal myocardial contractility, operated under MIRM conditions. Materials and methods. A comparative analysis of the immediate results of surgical treatment of 302 patients with coronary artery disease who underwent beating heart bypass surgery was carried out. Most of the patients were men (81.3%). The average age of the general group was 59.2 ± 7.4 years. The patients were divided into two groups - patients with LVEF less than 45% - 49 patients (16%) and patients with LVEF more than 45% - 253 people (84%). Results. Despite the fact that for a number of clinical indicators (concomitant diseases), we obtained a statistically significant difference - arterial hypertension, BCA lesion, mean LVEF, according to the main hemodynamic criteria, such as - unstable angina pectoris, middle class according to CCS and NYHA, the number of women in group, lesion of the trunk of the LCA and multivessel coronary artery disease, we did not reveal statistically significant differences between our groups. Nevertheless, the initial degree of operational risk according to EuroSCORE II was significantly higher in the first group of patients - with a low left ventricular ejection fraction. Conclusions. Our results of a comparative assessment of two groups of patients - with reduced LV ejection fraction (less than 45%) and with normal contractile ability, who underwent minimally invasive myocardial revascularization, showed the high efficiency of this type of surgical treatment.

Platelet aggregability and anticoagulant proteins activity during dobutamine stress echocardiography in asymptomatic patients four months after percutaneous coronary intervention

Introduction: Platelets aggregability (PA) and the activation of hemostasis, during myocardial ischemia within physical or mental stress, can be one of many factors that influence the process of stent thrombosis after percutaneous coronary intervention (PCI). Objective: The aim of the study is to investigate the relationship between PA and activity of anticoagulant proteins with myocardial ischemia during dobutamine stress echocardiography (DSE) in asymptomatic patients four months after PCI. Methods: The study population included 74 asymptomatic patients who had successful PCI four months before high-dose dobutamine stress echocardiography (DSE).PA on epinephrine (EPI) and adenosine diphosphate (ADP) were determined by Light Transmission Aggregometry (LTA), together with plasma activity of protein C (PC) and antithrombin (AT) before DSE and at the peak stage of the stress test. Patients were divided into several groups whether they have baseline or induced disturbance of segmental myocardial kinetics or not. All patients were on clopidogrel and aspirin therapy at the time of DSE. Results: There were no statistically significant difference in PA on ADP (47.50% vs. 50.20%; p=0.970) as well as on EPI (59.30% vs. 60.30%, p=0.600) before and at the peak DSE. A statistically significant difference was found in the anticoagulant activity of the AT (84.85% vs. 74.75%, p=0.001) and PC (77.75% vs. 67.60%, p<0.001). Significance of differences in antithrombin and the protein C, refers to the result before and at the peak levels of the test. There was no significant difference in PA and plasma activity of anticoagulant proteins in patients with or without induced myocardial ischemia at the peak of DSE. Patients who had increased wall motion score index (WMSI) at the peak of DSE had higher EPI induced PA (68.60% vs. 54.70% p=0.017) than patients with normal myocardial contractility. Conclusion: There are no changes in the PA before and after DSE, however, plasma activity of anticoagulant proteins decreased at the peak level of the test. Platelet aggregability on EPI significantly increases at the peak of DSE in patients with segmental myocardium hypocontractility.

Severe Hypocalcemia and Extreme Elevation of Serum Creatinkinase in a 16-Year Old Boy with Pseudohypoparathyroidism Type Ib

Calcium is essential for proper muscular function and metabolism. Myopathy with high creatinkinase activity can be a rare manifestation of hypocalcemia of various origin, such as vitamin D deficiency, hypoparathyroidism, pseudohypoparathyroidism (PHP). 16-year old previously healthy boy was admitted to intensive care unit with convulsions lasting for three minutes and a transient loss of consciousness. Laboratory results revealed severe hypocalcemia (total S-Ca < 1.0 mmol/L; normal 2.2-2.6 mmol/L), hyperphosphatemia (S-P 2.8 mmol/L; normal 0.6-1.6 mmol/L). Serum creatinkinase (S-CK) activity was 32 μkat/L (normal 0.57-2.45 μkat/L). Other basic biochemical parameters including creatinine, troponin, alkaline phosphatase were within normal values. Calcemia was gradually corrected within two weeks by intravenously and orally administered calcium and by cholecalciferol. S-CK reached a maximum of 222 μkat/L on day 4 and dropped to 7.2 μkat/L on day 14. Boy had no myalgias, neither clinical signs of myopathy. Echocardiography was normal with normal myocardial contractility, without any signs of calcification. The serum level of parathyroid hormone (S-PTH) was high (12 pmol/L; normal 0.7-5.5 pmol/L), fully compatible with the diagnosis of PHP. Molecular analysis revealed pseudohypoparathyroidism type Ib (PHPIb).In conclusion, manifest tetany and even mild myopathy with very high S-CK can occur in hypocalcemic patients and usually resolves after normalization of hypocalcemia.

PI3Kα is essential for the recovery from Cre/tamoxifen cardiotoxicity and in myocardial insulin signalling but is not required for normal myocardial contractility in the adult heart.

Genetic mouse models have yielded conflicting conclusions about the role of PI3Kα in heart physiology: specifically, the question of whether PI3Kα has a direct role in regulating myocardial contractility. This has led to concerns that PI3K inhibitors currently in clinical trials for cancer may potentiate cardiotoxicity. Here we seek to clarify the role of PI3Kα in normal heart physiology and investigate changes in related signalling pathways. Targeted deletion of PI3Kα and PI3Kβ in the heart with a tamoxifen-dependent Cre recombinase transgene caused transient heart dysfunction in all genotypes, but only PI3Kα deletion prevented functional recovery. Reduction in tamoxifen dosing allowed for maintained gene deletion without any cardiomyopathy, possibly through activation of survival signalling through the related ERK pathway. Similarly, mice with PI3Kα deletion induced by constitutively active Cre recombinase had normal heart function. Insulin-mediated activation of Akt, a marker of PI3Kα activity, was impaired with increased ERK1/2 activation in PI3Kα mutant hearts. Pharmacological inhibition of PI3Kα with BYL-719 also caused impaired insulin signalling in murine and human cardiomyocytes as well as in vivo in mice, with increased fasting blood glucose levels, but did not affect myocardial contractility as determined by echocardiography and invasive pressure-volume loop analysis. Our results show that PI3Kα does not directly regulate myocardial contractility, but is required for recovery from tamoxifen/Cre toxicity. The important role for PI3Kα in insulin signalling and recovery from tamoxifen/Cre toxicity justifies caution when using PI3Kα inhibitors in combination with other cardiovascular comorbidities and cardiotoxic compounds in cancer patients.

Assessment of Ventricular Function in Adults with Sickle Cell Disease: Role of Two-Dimensional Speckle-Tracking Strain

Sickle cell disease (SCD) is a hemoglobinopathy that is common worldwide. It usually presents with cardiac involvement, although data on systolic function are somewhat controversial. The aim of this study was to investigate the value of speckle-tracking strain, a deformation index, in detecting ventricular dysfunction in SCD. Ninety adult patients with SCD were compared with 20 healthy controls. Doppler echocardiography with Doppler tissue imaging was performed in all, and the left and right ventricles were analyzed by the use of two-dimensional speckle-tracking strain. The mean age of the patients with SCD was 26years, and 43% were men. Left ventricular (LV) dimensions and mass were higher in patients with SCD, whereas LV ejection fraction did not differ from the controls. E and A waves, as well as E/e' ratio, were also higher in patients with SCD. Two-dimensional speckle-tracking strain of both ventricles in the patients with SCD was not different from that of controls. The factors independently associated with LV longitudinal strain were age (P=.009), oximetry (P=.001), lactate dehydrogenase (P=.014), LV ejection fraction (P<.001), and right ventricular systolic annular velocity (P=.010). Ventricular enlargement with normal ventricular function was a frequent finding in SCD. Two-dimensional speckle-tracking strain of both ventricles was similar in patients and controls, suggesting normal myocardial contractility in patients with SCD. LV global longitudinal strain was associated with age, intensity of hemolysis, and ventricular function.

Assessment of myocardial oxygenation with MRI.

As an aerobic organ in a living body, the beating heart relies almost exclusively on the oxidation of energy-providing substrates such as free fatty acids (60-90%) for its primary contractile function. Specifically, chemical energy is generally produced in aerobic metabolic pathways through oxidative phosphorylation of ADP to ATP. Myocytes utilize the chemical energy stored in ATP molecules and transform it into mechanical energy. Accordingly, cardiac cells have to consume large amounts of O 2 for the contraction process, which accounts for over 80% of oxygen cost. The remaining <20% is consumed by other physiological processes not directly associated with contraction, i.e., membrane depolarization and repolarization. For this reason, the heart can only develop a small oxygen debt. Oxygen supply and demand has to match to maintain normal myocardial contractility.

Perioperative Therapeutic Plasmapheresis

Perioperative Therapeutic Plasmapheresis

793 Management of Acute Circulatory Failure in Children Based on the Evaluation by Echocardiography in Pediatric Intensive Care Unit (PICU)

Background and AimsEchocardiography has an important role to perform in the PICU, as it is an efficient, accurate, non invasive diagnostic modality that can aid the intensivist in the management...

The dynamic role of cardiac myosin binding protein-C during ischemia

Cardiac myosin binding protein C (cMyBP-C) is a myofibrillar protein important for normal myocardial contractility and stability. In mutated form it can cause cardiomyopathy and heart failure. cMyBP-C appears to have separate regions for different functions. Three phosphorylation sites near the N terminus modulate contractility by their effect on both the kinetics of contraction and the binding site of the N-terminus. The C terminal region binds to myosin rods and stabilizes thick filament structure. The aim of the study reported here was to test whether cMyBPC is important in producing the structural and functional changes that result from ischemia/reperfusion. In this study the sequential changes in cMyBP-C, contractility, and thick filament structure following dephosphorylation of cMyBP-C associated with ischemia and reperfusion have been studied in biopsied specimens from chronically instrumented dogs. One and two dimensional electrophoresis, electron microscopy and immunocytochemistry with multiple antibodies generated against different domains in cMyBP-C have been used to follow structural changes in cMyBP-C. Ischemia produced dephosphorylation of cMyBP-C. Subsequent reperfusion released the dephosphorylated cMyBP-C from myofibrils and activated proteolysis of the cytoplasmic cMyBP-C. This in turn leads to increased vulnerability of cMyBP-C to proteolysis and increased degradation of thick filaments. The state of cMyBP-C appears to be closely related to phosphorylation and dephosphorylation of serine 282. In the absence of the stabilizing action of cMyBP-C either as a consequence of genetic mutation or dephosphorylation, premature degradation of thick filaments occurs and is accompanied by persistent contractile dysfunction.

N-terminal Pro brain natriuretic peptide is a reliable biomarker of reduced myocardial contractility in patients with lamin A/C gene mutations

BackgroundRecently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations. MethodsWe prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age–sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE). ResultsTwenty-three patients were included (10 males, mean age 39.2±18.9years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123±229 versus 26±78pg/ml, p=0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341±1032pg/ml versus 80±79pg/ml in patients with normal myocardial contractility, p=0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697–1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125pg/ml. ConclusionNT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients.

Treatment of Isolated Left Ventricular Diastolic Dysfunction in Hypertension

Arterial hypertension is a major risk factor for congestive heart failure. Left ventricular (LV) hypertrophy is often associated with arterial hypertension and characterizes subjects with a particularly elevated risk of untoward cardiovascular events, including heart failure.1 LV hypertrophy is, in turn, associated with impaired LV myocardial contractility and LV diastolic dysfunction. LV hypertrophy, impaired LV myocardial contractility, and LV diastolic dysfunction predict heart failure in population-based studies.2,3 Subjects with heart failure but with normal LV ejection fraction, that is, with diastolic heart failure, exhibit abnormal LV diastolic function.4 However, Doppler parameters of LV diastolic function may be abnormal in the absence of overt heart failure. Such a condition, called “isolated LV diastolic dysfunction,” bears independent prognostic significance in population-based and clinical studies.2,3,5 Thus, regression of isolated LV diastolic dysfunction may be considered an important therapeutic target in hypertension. In the general adult population without congestive heart failure, ≈30% may show LV diastolic dysfunction of any degree.6 In high-risk subgroups (patients >65 years of age, those with hypertension, and those with LV hypertrophy), the prevalence of isolated LV diastolic dysfunction rises to 60–80%.7 On the other hand, LV diastolic dysfunction may be found in ≈26% of hypertensive subjects without LV hypertrophy and with normal myocardial contractility.8 LV hypertrophy regression, proven to be protective in hypertension,9 is a major determinant of LV diastolic dysfunction regression in hypertensive subjects.7 However, it remains to be explored whether isolated LV diastolic dysfunction …

Alteration of messenger RNA and protein levels of cardiac alpha(1)-adrenergic receptor and angiotensin II receptor subtypes during aging in rats

Structural and functional alterations in the senescent heart have been associated with an activated sympathetic nervous system and a regional cardiac renin-angiotensin system. To date, however, limited information related to their expression alteration during the whole procress of growth and development has been reported. To examine the expression of alpha(1)-adrenergic receptor (alpha(1)-AR) and angiotensin II receptor (ATR) subtypes in the left ventricle of hearts from young adult, middle-aged, presenescent and senescent rats. Semiquantitative reverse transcriptase polymerase chain reaction and Western blot were used to quantitate the messenger RNA and protein of alpha(1)-AR and ATR subtypes, respectively, in the left ventricles of three- (young adult), 12- (middle age), 18- (presenescent) and 24-month-old (senescent) Wistar rats. alpha(1A)-AR expression decreased gradually with age, and alpha(1D)-AR expression was repressed in middle age and presenescence, while the expression of alpha(1B)-AR remained unchanged during senescence. AT(1)R expression was unaffected by aging from young adulthood to presenescence, but exhibited a remarkable upregulation in senescence. There were no significant discrepancies of cardiac AT(2)R expression among the four age groups, but both messenger RNA and protein had a tendency to upregulate during aging. The results suggest that there are considerable changes of expression of cardiac alpha(1)-AR and ATR subtypes during growth and development. The change of cardiac alpha(1)-AR and ATR expression during aging is a protective response to senescence by keeping normal myocardial contractility, while the upregulation of AT(1)R and AT(2)R promotes age-related myocardium hypertrophy and cardiac remodelling.

Occult cardiac dysfunction in patients with obstructive sleep apnea syndrome revealed by tissue Doppler imaging

Obstructive sleep apnea syndrome has been linked to cardiovascular complications. The diagnosis of effects of sleep apnea on heart may be difficult before apparent examination findings. The aim of the present study was to evaluate changes of myocardial contractile properties in patients affected by sleep apnea showing tissue Doppler imaging, in the face of quite normal myocardial contractility on standard echocardiography. Shortly, tissue Doppler imaging may represent an early stage of myocardial abnormality despite a preserved global function.

Sudden cardiac death in athlete with anomalous single coronary artery

A 43-year-old Caucasian male and avid runner was referred to our institution for evaluation after an episode of exercise-induced syncope. Treadmill testing was complicated by cardiac arrest at peak exercise with polymorphic ventricular tachycardia (Fig. 1) that was successfully cardioverted. Baseline transthoracic echocardiogram revealed no evidence of structural disease with normal myocardial contractility. Cardiac catheterization demonstrated an anomalous coronary artery arising from a single ostium in the right aortic sinus of Valsalva (Fig. 2), dividing into

第3度房室ブロックを呈した犬にVVI型ペースメーカー植え込み術を行った1例

Electrocardiograms of a 6-year-old male Chesapeake Bay Retriever with a history of depression and anorexia revealed critical bradycardia, and disassociation of P waves (166 beats/min) and QRS complexes (20beats/min). Antiarrythmic medical therapy had no effect, and echocardiograms revealed normal myocardial contractility. From these findings, we diagnosed the dog as having a third-degree atrioventricular block. The animal was anesthetized, and a permanent artificial epicardial WI pacemaker was implanted under temporary transvenous endocardial pacing. Anesthetic and postoperative recovery was uneventful, and clinical signs improved immediately. Twelve months after the implantation, the patient was doing well with no clinical signs and no medication. This case suggests that the risk involved in general anesthesia for implantation due to bradycardia can be avoided by means of temporary transvenous endocardial pacing.

Left ventricular remodeling, mechanics, and tissue characterization in congenital aortic stenosis

Background: As the response of the myocardium to pressure overload is age-dependent, this study was designed to examine left ventricular (LV) remodeling, mechanics, and tissue characterization in children with moderate congenital aortic stenosis. Methods: We studied by echocardiography Doppler 22 patients (mean age 12.4 ± 5.6 years) with peak and mean transvalvular gradient of 63 ± 6 and 32 ± 4 mm Hg, respectively. In addition, 30 age- and body surface area-matched participants with structurally normal hearts were used as a control group. Sex- and age-specific cut-off levels for LV mass/height2.7 and relative wall thickness were defined to assess LV geometry. As a load-independent index of myocardial contractility, the relation between the rate-corrected velocity of circumferential fiber shortening both at endocardium and midwall, and meridional end-systolic stress was assessed. In addition, LV diastolic function was also evaluated by the mitral flow indexes. Finally, ultrasonic tissue characterization of the LV myocardium was performed by calculating the magnitude of cyclic variation, which reflects the intramural contractile function, and the averaged myocardial intensity of integrated backscatter, which is directly related to the myocardium collagen content. Results: The endocardial velocity of circumferential fiber shortening endocardium and meridional end-systolic stress relationship was within the normal range (mean ± 2SD) in 18 of 22 patients (81.8%), and midwall velocity of circumferential fiber shortening at endocardium and meridional end-systolic stress was normal in all 22 patients. No mitral flow index of LV diastolic function was significantly different between aortic stenosis group and normal participants. In our study population, 16 of 22 patients (72.7%) showed normal LV geometry, 3 (13.6%) had a pattern of concentric remodeling, and 3 (13.6%) concentric hypertrophy. LV hypertrophy was not marked (left ventricular mass index [LVMI] < 51 g/m2.7) in any patient. Finally, compared with control participants our study population showed, both at interventricular septum and posterior wall, comparable values of cyclic variation integrated backscatter, but significantly higher values of averaged myocardial integrated backscatter intensity (P <.01). Conclusions: In children with moderate congenital aortic stenosis, the total amount of myocardial collagen was increased despite normal LV myocardial contractility and diastolic function. Furthermore, LV remodeling was abnormal in only about a quarter of our patients and none had more than mild hypertrophy. Although the majority of these patients do not have markers now recognized to predict higher risk of cardiovascular events, the long-term significance of myocardial fibrosis and its response to treatment remain to be investigated. (J Am Soc Echocardiogr 2003;16:214-20.)

Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2.

Ventricular septal defects are common in human infants, but the genetic programs that control ventricular septation are poorly understood. Here we report that mice with a targeted disruption of the cardiovascular basic helix-loop-helix factor (CHF)1Hey2 gene show isolated ventricular septal defects. These defects result primarily in failure to thrive. Mice often succumbed within the first 3 wk after birth and showed pulmonary and liver congestion. The penetrance of this phenotype varied, depending on genetic background, suggesting the presence of modifier genes. Expression patterns of other cardiac-specific genes were not affected. Of the few animals on a mixed genetic background that survived to adulthood, most developed a cardiomyopathy but did not have ventricular septal defects. Our results indicate that CHF1 plays an important role in regulation of ventricular septation in mammalian heart development and is important for normal myocardial contractility. These mice provide a useful model for the study of the ontogeny and natural history of ventricular septal defects and cardiomyopathy.

The Physiological and Pharmacological Significance of Cardiovascular T-Type, Voltage-gated Calcium Channels

An influx of calcium ions into cells, made possible by the opening of specific, voltage-gated channels, triggers muscular contraction and several other physiological processes. Two types of calcium channels, L-type and T-type, are found in the cardiovascular system. These two types of channels differ considerably in their electrical and chemical characteristics and in their distribution in tissue. The L-type calcium channel is responsible for normal myocardial contractility and for vascular smooth muscle contractility. In contrast, T-type calcium channels are not normally present in the adult myocardium, but are prominent in conducting and pacemaking cells. They are thought to help regulate vascular tone, signal conduction, cardiac pacemaking, and the secretion of certain intercellular transmitters. T-Type channels also seem to have an important role in normal growth processes and in the tissue remodeling that occurs in pathologic processes such as cardiac hypertrophy. Traditional calcium antagonists act on L-type channels. Mibefradil is a recently characterized calcium antagonist and the first that is selective for T-type calcium channels. This unique property may lead to major applications in cardiovascular medicine.