Mechanisms underlying ischemic diastolic dysfunction: relation between rigor, calcium homeostasis, and relaxation rate

2003 ◽  
Vol 284 (3) ◽  
pp. H758-H771 ◽  
Author(s):  
Niraj Varma ◽  
James P. Morgan ◽  
Carl S. Apstein
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Coronary Flow ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Relaxation Cycle ◽  
Relaxation Velocity ◽  
Butanedione Monoxime ◽  
Length Changes ◽  
Severe Ischemia

Increased diastolic chamber stiffness (↑DCS) during ischemia may result from increased diastolic calcium, rigor, or reduced velocity of relaxation. We tested these potential mechanisms during severe ischemia in isolated red blood cell-perfused isovolumic rabbit hearts. Ischemia (coronary flow reduced 83%) reduced left ventricular (LV) contractility by 70%, which then remained stable. DCS progressively increased. When LV end-diastolic pressure had increased 5 mmHg, myofilament calcium responsiveness was altered with 50 mmol/l NH4Cl or 10 mmol/l butanedione monoxime. These affected contractility (i.e., a calcium-mediated force) but not ↑DCS. Second, quick length changes reversed ↑DCS, supporting a rigor mechanism. Third, ischemia increased the time constant of isovolumic pressure decline from 47 ± 3 to 58 ± 3 ms ( P < 0.02) but concomitantly abbreviated the contraction-relaxation cycle, i.e., pressure dissipation occurred earlier without diastolic tetanization. Finally, to assess any link between rate of relaxation and ↑DCS, hearts were exposed to 10 mmol/l calcium. Calcium doubled contractility and accelerated relaxation velocity, but without affecting ↑DCS. Thus ↑DCS developed during ischemia despite severely reduced contractility via a rigor (and not calcium mediated) mechanism. Calcium resequestration capacity was preserved, and reduced relaxation velocity was not linked to ↑DCS.

Effect of anemia on cardiac function, microvascular structure, and capillary hematocrit in rat hearts

2001 ◽  
Vol 280 (3) ◽  
pp. H1407-H1414 ◽  
Author(s):  
Karel Rakusan ◽  
N. Cicutti ◽  
F. Kolar
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Diastolic Pressure ◽  
Experimental Situation ◽  
Young Male ◽  
Left Ventricular ◽  
Male Rats ◽  
Capillary Length ◽  
Chronic Anemia ◽  
Cell Spacing

The effect of anemia on the coronary microcirculation was studied in young male rats. Chronic anemia resulted in increased left ventricular end-diastolic pressure and decreased functional reserve. Cardiac mass in anemic animals increased by 25%. Capillary and arteriolar densities in these hearts remained unchanged, indicating angiogenesis in this experimental situation (estimated aggregate capillary length in the left ventricle of anemic hearts was 3.06 km compared with 2.35 km in control hearts). Capillary hematocrit was decreased in chronic anemia less than systemic hematocrit: from 25 to 18% in anemia versus 45 to 28% in controls. Capillary hematocrit and red blood cell spacing were also studied after acute blood withdrawal. Here, capillary hematocrit was preserved even more: 22 versus 24% in systemic hematocrit. Finally, the same was studied in isolated hearts perfused with solutions of various hematocrits. After perfusion with low-hematocrit solution (14%), the capillary hematocrit (24%) was even higher than the perfusate hematocrit! In conclusion, we found evidence of angiogenesis in cardiomegaly induced by chronic anemia. Microvascular growth was accompanied by advantageous regulation of red blood cell spacing within these vessels. This was even more pronounced during acute hemodilution and in isolated perfused hearts.

In vivo microvascular structural and functional consequences of muscle length changes

1997 ◽  
Vol 272 (5) ◽  
pp. H2107-H2114 ◽  
Author(s):  
D. C. Poole ◽  
T. I. Musch ◽  
C. A. Kindig
Keyword(s):  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Oxygen Delivery ◽  
Sarcomere Length ◽  
Flow Dynamics ◽  
Capillary Diameter ◽  
Luminal Diameter ◽  
Length Changes

As muscles are stretched, blood flow and oxygen delivery are compromised, and consequently muscle function is impaired. We tested the hypothesis that the structural microvascular sequellae associated with muscle extension in vivo would impair capillary red blood cell hemodynamics. We developed an intravital spinotrapezius preparation that facilitated direct on-line measurement and alteration of sarcomere length simultaneously with determination of capillary geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere lengths achievable in vivo was 2.17 +/- 0.05 to 3.13 +/- 0.11 microns. Capillary tortuosity decreased systematically with increases of sarcomere length up to 2.6 microns, at which point most capillaries appeared to be highly oriented along the fiber longitudinal axis. Further increases in sarcomere length above this value reduced mean capillary diameter from 5.61 +/- 0.03 microns at 2.4-2.6 microns sarcomere length to 4.12 +/- 0.05 microns at 3.2-3.4 microns sarcomere length. Over the range of physiological sarcomere lengths, bulk blood flow (radioactive microspheres) decreased approximately 40% from 24.3 +/- 7.5 to 14.5 +/- 4.6 ml.100 g-1.min-1. The proportion of continuously perfused capillaries, i.e., those with continuous flow throughout the 60-s observation period, decreased from 95.9 +/- 0.6% at the shortest sarcomere lengths to 56.5 +/- 0.7% at the longest sarcomere lengths and was correlated significantly with the reduced capillary diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary geometry and luminal diameter consequent to increased muscle sarcomere length are associated with a reduction in mean capillary red blood cell velocity and a greater proportion of capillaries in which red blood cell flow is stopped or intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen) delivery, it also alters capillary red blood cell flow dynamics, which may further impair blood-tissue oxygen exchange.

Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs

1990 ◽  
Vol 258 (4) ◽  
pp. H1250-H1254 ◽  
Author(s):  
A. Chu ◽  
D. E. Chambers ◽  
C. C. Lin ◽  
W. D. Kuehl ◽  
F. R. Cobb
Keyword(s):  
Nitric Oxide ◽  
Coronary Flow ◽  
Diastolic Pressure ◽  
Coronary Vessels ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Vasomotor Tone ◽  
Coronary Vasomotor Tone ◽  
Endogenous Nitric Oxide

This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance.

P1718Veno-arterial ECMO versus Left Impella bleeding complications in cardiogenic shock patients on dual antiplatelet therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Vandenbriele ◽  
J Wilson ◽  
A Baker ◽  
A Azzu ◽  
A Gambaro ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cardiogenic Shock ◽  
Antiplatelet Therapy ◽  
Red Blood Cell ◽  
Dual Antiplatelet Therapy ◽  
Left Ventricular ◽  
Left Ventricular Failure ◽  
Ventricular Failure ◽  
Red Blood Cell Transfusions ◽  
Va Ecmo

Abstract Background Selective groups of patients, presenting with INTERMACS-1 cardiogenic shock due to acute ischaemic heart failure, may benefit from mechanical circulatory support (MCS). Patients with biventricular failure, severe septic shock or oxygenation problems should be selected for VA-ECMO, although the left Impella-CP heart pump can be considered as a less invasive alternative in supporting predominantly left ventricular failure. Bleeding issues are a major concern in patients on MCS, especially in this group where triple anticoagulation therapy (unfractionated heparin (UFH) for prevention of pump thrombosis and dual antiplatelet therapy (DAPT) after coronary stenting) is necessitated. We aim to investigate the bleeding and transfusion rate in DAPT-patients on VA-ECMO versus Impella. Methods We report single center data for 51 VA-ECMO and 8 Impella patients between 2011 and 2019. Indication for MCS was acute ischaemic cardiogenic shock. Patient demographics, transfusions and reported/radiographically diagnosed bleeding (BARC-classification) complications were analyzed. All patients received UFH and low dose aspirin plus clopidogrel or ticagrelor. Impella flow was at least 2.5 L/min. Transfusion targets were Hb >7 g/dl, fibrinogen >100 mg/dl (or >150 mg/dl when active bleeding) and platelet count >50/fL. Results Impella patients were significantly older (VA-ECMO 52.8 vs. Impella 62.4; p=0.02) as compared to the VA-ECMO group. Anti-Xa-levels and length of the MCS-run (mean 7.9 VA-ECMO vs. 6.4 days Impella) were comparable in both groups. Occurrences of minor bleeds was comparable between both groups (mainly oozing from the insertion site in the ImpellaTM group 63% vs. VA-ECMO 72%; p>0.05) but major bleedings with BARC score of 3 or more were significantly lower in the Impella group (13% vs. VA-ECMO 65%; p=0.005). Platelet and red blood cell transfusions were significantly lower in the Impella group (0.1 units of platelets per day vs. 1.1 units of platelets per day on VA-ECMO; p=0.002 and 0.8 units of RBCs per day vs. 2.6 units of RBCs per day on VA-ECMO; p=0.02). Bleeding/transfusion VA-ECMO vs Impella Conclusions Bleeding is a frequent complication of MCS. However, in our cohort, triple anticoagulation in acute cardiogenic shock due to ischaemic left ventricle failure resulted in a lower major bleeding rate when support was given by the left Impella device as compared with VA-ECMO therapy group. As a result, platelet and red blood cell transfusions were lower in the Impella group. These findings are likely to be partly explained by the increased number and size of cannulas in VA-ECMO, as well as the increased risk of haemolysis and consumptive coagulopathy due to the complexity and extensive foreign body surface of the ECMO-circuit. We conclude that Impella support should be considered as a safer option than VA-ECMO with regards to bleeding in patients with ischaemic left ventricular failure who require DAPT and MCS as a bridge to recovery or other definitive therapy.

Direct cardiac effects of vasopressin and their reversal by a vascular antagonist

1986 ◽  
Vol 251 (4) ◽  
pp. H734-H741 ◽  
Author(s):  
W. A. Boyle ◽  
L. D. Segel
Keyword(s):  
Coronary Flow ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Total Output ◽  
Stroke Work ◽  
Cardiac Effects ◽  
Myocardial O2 Consumption ◽  
Dose Dependent

We studied the direct cardiac effects of arginine vasopressin (AVP) by use of an isolated working rat heart model perfused with Krebs-Henseleit medium. At a concentration of 878 +/- 15 pg/ml, AVP produced significant (P less than 0.05) decreases in coronary flow (-31 +/- 2%); myocardial O2 consumption (-12 +/- 2%); left ventricular peak systolic pressure (-5 +/- 1%); dP/dtmax (-7 +/- 1%); -dP/dtmax (-6 +/- 3%); peak aortic flow rate (-5 +/- 1%); stroke work (-3 +/- 1%); peak power (-8 +/- 1%); and total output (-3 +/- 1%). Aortic output increased significantly (+7 +/- 1%) as did arteriovenous O2 difference (+108 +/- 14 mmHg); left ventricular end-diastolic pressure (+0.4 +/- 0.1 mmHg); efficiency (+1.5 +/- 0.4%); and rate of lactate release (+1.27 +/- 0.21 nmol/ml perfusate/min). Dose-response relationships were studied at 9 +/- 1, 25 +/- 1, 75 +/- 3, 303 +/- 15, and 817 +/- 42 pg AVP/ml. Significant dose-dependent depression of coronary flow occurred at the three highest AVP concentrations; cardiac function was significantly depressed at the highest dose. The AVP analogue d(CH2)5[Tyr(Me)]AVP (20 ng/ml) completely reversed the cardiac effects attributed to AVP. The data indicate that AVP is a potent direct coronary constrictor that produces myocardial ischemia and decreased contractile function at AVP concentrations that are observed in some pathophysiologic states.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociation of myocardial sodium and potassium alterations in mild versus severe ischemia

1980 ◽  
Vol 238 (4) ◽  
pp. H575-H580
Author(s):  
T. J. Regan ◽  
L. Broisman ◽  
B. Haider ◽  
C. Eaddy ◽  
H. A. Oldewurtel
Keyword(s):  
Diastolic Pressure ◽  
Major Effect ◽  
Left Ventricular ◽  
Cell Permeability ◽  
Water Composition ◽  
Ischemic Tissue ◽  
Group A ◽  
Anesthetized Dogs ◽  
Group B ◽  
Severe Ischemia

To determine the relative influence of two levels of ischemia on myocardial cation and water composition as well as cardiac function, intact anesthetized dogs were studied for 1 h using a balloon-tip catheter in the proximal left anterior descending coronary artery. Hemodynamic studies in group A revealed a diminished ejection fraction during mild and severe ischemia associated, respectively, with a 36% and 74% decline in transmural coronary flow. Left ventricular end diastolic pressure rose only after severe ischemia. Greater accumulation of sodium and water and loss of K+ in ischemic tissue was observed in animals with severe ischemia. In group B, intracellular cations and water were estimated on the basis of 51Cr-labeled EDTA distribution. The extracellular space was unaltered at either level of ischemia. During mild ischemia, cell Na+ and H2O were enhanced in the inner and outer layers of myocardium. Despite a 25% reduction in subendocardial blood flow by the labeled microsphere technique, K+ content was normal. After severe ischemia, cell K+ was reduced in inner and outer layers. However, the increase of cell Na+ content substantially exceeded K+, suggesting a major effect on the sodium pump or cell permeability.

Evaluation of Cardial Iron Deposition by T2* MRI in Transfusion Dependent Patients with Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2663-2663
Author(s):  
Simona Deplano ◽  
Anna Di Tucci ◽  
Gildo Matta ◽  
Annalisa Agus ◽  
Attilio Gabbas ◽  
...  
Keyword(s):  
Blood Cell ◽  
Serum Ferritin ◽  
Red Blood Cell ◽  
Myelodysplastic Syndromes ◽  
Cardiac Mri ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Red Blood Cell Transfusion ◽  
Myocardial Iron

Abstract Cardiac T2* Magnetic Resonance Imaging (MRI) has been recently used to evaluate myocardial iron deposition in patients with transfusion dependent beta-thalassemia major. No comparable studies have been published for patients with myelodysplastic syndromes receiving chronic red blood cell transfusion. Therefore we measured cardiac-MRI T2* in 16 patients (10 male, 6 female) with myelodysplastic syndromes (aged 54 – 82 years, median age 67). All of them were transfusion dependent having received a median number of 60 (range 16–225) packed red blood cell transfusion equivalent to 3.2 – 45 (median 12) grams of iron. Nine have been irregularly and sporadically chelated by deferoxamine, seven were unchelated. Serum ferritin levels ranged from 1163 to 6241 mg/dl (median value 2086). None of the patients presented signs or symptoms of cardiac dysfunction at the time of the study. Cardiac-MRI T2*values obtained ranged from 5.6 to 80 (median value 46.5) milliseconds (ms). Correlation between serum ferritin and cardiac T2* value was weak ( r= 0.43, r2 =0.18). According to D. Pennel we considered as significant of myocardial iron deposition a relaxation time ≤ 20ms. Cardiac T2* was < 20ms in 3 patients who had never used iron chelators (5.6, 12.4 and 8.5 ms, respectively). They had received 39, 101 and 200 units of red blood cell transfusion, corresponding to 7.8, 20 and 40 grams of iron, respectively. Of relevance 2 of them died within few months after the end of the study and one showed early signs of left ventricular dysfunction. None of the patients with a cardiac T2* value >20 ms showed instrumental nor clinical signs of cardiac deterioration in six months follow up. No patient who had received less than 39 transfusions presented cardiac T2* value ≤20 ms. Evaluation of myocardial iron deposition by T2* cardiac MRI could be recommendable in myelodyplasia patients who had received more than 30 packed red blood cells transfusisions.

Reduced oxygen supply explains the negative force-frequency relation and the positive inotropic effect of adenosine in buffer-perfused hearts

2005 ◽  
Vol 289 (1) ◽  
pp. H131-H136 ◽  
Author(s):  
Rodrigo M. Marin ◽  
Kleber G. Franchini
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Oxygen Supply ◽  
Positive Inotropic Effect ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Frequency Relation ◽  
Perfused Hearts

In isolated rat hearts perfused with HEPES and red blood cell-enriched buffers, we examined changes in left ventricular pressure induced by increases in heart rate or infusion of adenosine to investigate whether the negative force-frequency relation and the positive inotropic effect of adenosine are related to an inadequate oxygen supply provided by crystalloid perfusates. Hearts perfused with HEPES buffer at a constant flow demonstrated a negative force-frequency relation, whereas hearts perfused with red blood cell-enriched buffer exhibited a positive force-frequency relation. In contrast, HEPES buffer-perfused hearts showed a concentration-dependent increase in left ventricular systolic pressure [EC50 = 7.0 ± 1.2 nM, maximal effect (Emax) = 104 ± 2 and 84 ± 2 mmHg at 0.1 μM and baseline, respectively] in response to adenosine, whereas hearts perfused with red blood cell-enriched buffer showed no change in left ventricular pressure. The positive inotropic effect of adenosine correlated with the simultaneous reduction in heart rate ( r = 0.67, P < 0.01; EC50 = 3.8 ± 1.4 nM, baseline 228 ± 21 beats/min to a minimum of 183 ± 22 beats/min at 0.1 μM) and was abolished in isolated hearts paced to suppress the adenosine-induced bradycardia. In conclusion, these results indicate that the negative force-frequency relation and the positive inotropic effect of adenosine in the isolated rat heart are related to myocardial hypoxia, rather than functional peculiarities of the rat heart.

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