Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy.

Rakusan, K; Flanagan, Michael F.; Geva, Tal; Southern, James F.; Praagh, Richard Van

doi:10.1161/01.cir.86.1.38

Cited by 288 publications

(176 citation statements)

References 42 publications

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“…Cardiac hypertrophy decreases capillary density with as much as 30%,35 resulting in an increased diffusion distance from capillaries to cardiomyocytes 9, 36, 37. This exchange may be further hampered by deterioration of the coronary reserve in hypertrophic hearts1 and an increase in the extracellular collagen matrix leading to increased oxygen consumption 5.…”

Section: Discussionmentioning

confidence: 99%

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Nepper‐Christensen

Lønborg

Ahtarovski

et al. 2017

JAHA

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BackgroundApproximately one third of patients with ST‐segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association between LVH and: myocardial infarct size, area at risk, myocardial salvage, microvascular obstruction, left ventricular (LV) function (all determined by cardiac magnetic resonance [CMR]), and all‐cause mortality and readmission for heart failure in STEMI patients treated with primary percutaneous coronary intervention.Methods and ResultsIn this substudy of the DANAMI‐3 trial, 764 patients underwent CMR. LVH was defined by CMR and considered present if LV mass exceeded 77 (men) and 67 g/m2 (women). One hundred seventy‐eight patients (24%) had LVH. LVH was associated with a larger final infarct size (15% [interquartile range {IQR}, 10–21] vs 9% [IQR, 3–17]; P<0.001) and smaller final myocardial salvage index (0.6 [IQR, 0.5–0.7] vs 0.7 [IQR, 0.5–0.9]; P<0.001). The LVH group had a higher incidence of microvascular obstruction (66% vs 45%; P<0.001) and lower final LV ejection fraction (LVEF; 53% [IQR, 47–60] vs 61% [IQR, 55–65]; P<0.001). In a Cox regression analysis, LVH was associated with a higher risk of all‐cause mortality and readmission for heart failure (hazard ratio 2.59 [95% CI, 1.38–4.90], P=0.003). The results remained statistically significant in multivariable models.ConclusionsLVH is independently associated with larger infarct size, less myocardial salvage, higher incidence of microvascular obstruction, lower LVEF, and a higher risk of all‐cause mortality and incidence of heart failure in STEMI patients treated with primary percutaneous coronary intervention.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01435408.

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Section: Discussionmentioning

confidence: 99%

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Nepper‐Christensen

Lønborg

Ahtarovski

et al. 2017

JAHA

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“…In many studies, (e.g., Anversa et al, 1980;Cluzeaut and Maurerschultze, 1986;Olivetti et al, 1987;Olivetti et al, 1989;Rakusan et al, 1992), the investigators estimated the densities of capillary and cardiomyocyte structural quantities. Biological conclusions based on density measurements alone are very difficult to interpret because it will never be made known if changes in the density are due to a change in total structural quantity and/or a change in the reference volume.…”

Section: Discussion the Importance Of Estimating Total Quantitymentioning

confidence: 99%

“…Especially, the myocytes and capillaries in the heart have been the focus of many cardiovascular research articles (e.g., Loud et al, 1978;Anversa et al, 1980;Tomanek et al, 1986;Olivetti et al, 1987;Rakusan et al, 1992;Gerdes et al, 1994;Austin et al, 1995;Mayhew et al, 1997;Pessanha and Mandarim-deLacerda, 2000;Van Vre et al, 2007). The principal goal of most of these studies was to provide quantitative information on the changes in heart morphology and function under various conditions, for example, during development, aging, left ventricular hypertrophy, and following ischemia/reperfusion.…”

mentioning

confidence: 99%

The Application of Stereological Methods for Estimating Structural Parameters in the Human Heart

Tang

Nyengaard

Andersen

et al. 2009

The Anatomical Record

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This study describes and exemplifies generally applicable designbased stereological methods for obtaining quantitative estimates of the numbers and sizes of capillaries, cardiomyocytes, and cardiomyocyte nuclei in immersion-fixed human left ventricles (N ¼ 6). The design-based stereological methods are valid in all cardiac investigations onto quantifying changes in structure and function as seen under various conditions such as during development, aging, hypertrophy, and following ischemia/ reperfusion. The applied principles of unbiased stereology were as follows: 1) uniform random sampling was taken at all levels, also in respect to orientations, for estimates of length and mean sizes. 2) All global structural quantities were estimated as total quantity ¼ density Â volume of the left ventricle. As an example, the left ventricle contains 1.5 Â 10 9 capillaries with a total length of just below 200 km. 3) Stereological methods were used for estimating the volume density, surface area density, and length density of capillaries and cardiomyocytes. The numerical density of cardiomyocyte nuclei and capillaries was estimated, using the optical and physical disector, respectively. 4) In all local quantities, ''size'' was estimated either directly, using unbiased estimators to obtain the average individual size and size distribution parameters, or indirectly, using the relationship that: average size ¼ total quantity/total number. In the six hearts constituting this study, we observed the anticipated correlation between left ventricular volume and global estimates such as total number of capillaries. There were no correlation between local quantities and total left ventricular volume (e.g., average star volume of individual cardiomyocytes). Anat Rec, 292:1630Rec, 292: -1647Rec, 292: , 2009. V V C 2009 Wiley-Liss, Inc.

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“…These cells are highly metabolic, requiring plenty of oxygen supply [3]. In MI, a blood vessel supplying a certain part of the heart becomes chronically clogged with plaque, up to a point when the cells in the affected region stop receiving adequate supply of oxygen.…”

Section: Myocardial Infarctionmentioning

confidence: 99%

Endothelial cells guided by immobilized gradients of vascular endothelial growth factor on porous collagen scaffolds

et al. 2011

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A key challenge in tissue engineering is overcoming cell death in the scaffold interior due to the limited diffusion of oxygen and nutrients therein. We hypothesized here that immobilizing a gradient of vascular endothelial growth factor would guide endothelial cells into the interior of the scaffold thereby enhancing angiogenesis. The protein was immobilized onto a collagen scaffold through carbodiimide chemistry by one of the three methods experimented: placing 5 µl of the solution at the center of the scaffold to create a ~2 ng/ml/mm gradient in a radial direction. D4T endothelial cells were observed to be guided by this VEGF-165 gradient deep into the center of the scaffold compared to both uniformly immobilized VEGF-165 and VEGFfree controls. We concluded that the VEGF-165 gradient scaffolds promoted the migration, and not proliferation, of cells deep into the scaffold. These gradient scaffolds provide the foundation for future in vivo tissue engineering studies.iii

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Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy.

Abstract: Pressure-overload left ventricular hypertrophy in children demonstrates proportional capillary angiogenesis, whereas in adults, hypertrophy appears to be associated with failure of compensatory angiogenesis.

Cited by 288 publications

References 42 publications

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

The Application of Stereological Methods for Estimating Structural Parameters in the Human Heart

Endothelial cells guided by immobilized gradients of vascular endothelial growth factor on porous collagen scaffolds

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