The time of onset and severity of acidosis in myocardial ischaemia

Cobbe, S. M.; Poole‐Wilson, Philip A.

doi:10.1016/0022-2828(80)90077-2

Cited by 235 publications

(75 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 1935, Tennant and Wiggers (1935) demonstrated that a reduction in coronary flow had a more profound effect on myocardial contractility than did hypoxia. The early decrease in contractile force of ischemic hearts was associated with increased tissue lactate and H + (Cobbe and Poole-Wilson, 1980;Jacobus et al, 1982) with little change in tissue ATP (Katz, 1969;Gudbjarnason et al, 1970;Neely et al, 1973;Hearse, 1979). The onset of irreversible damage was also related to the continued presence of high lactate levels .…”

Section: Discussionmentioning

confidence: 97%

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Neely¹,

Grotyohann²

1984

Circulation Research

547

162

View full text Add to dashboard Cite

SUMMARY. The mechanism of irreversible damage to ischemic myocardium was investigated in the perfused rat heart. The time of transition from reversible to irreversible damage to contractile function was accelerated by accumulation of glycolytic products and increases in extracellular calcium. Both of these effects were largely independent of adenine nucleotide levels in the tissue. With zero coronary flow and 1.25 nut calcium the decrease in ability of the heart to recover ventricular function with reperfusion after 30 minutes of ischemia was directly correlated with accumulation of glycolytic products (as estimated by tissue lactate) during ischemia. The extent of lactate accumulation during ischemia was varied by preperfusing the hearts for 0, 10, or 15 minutes under anoxic, high coronary flow conditions to deplete tissue glycogen prior to ischemia, and by adding lactate back to the perfusate of these hearts during the ischemic period. Recovery of ventricular function was inversely related to tissue lactate during ischemia and varied from 28 to 92%, even though there was little or no change in tissue levels of residual adenosine triphosphate. Increasing extracellular calcium accelerated the time of onset of irreversible damage with little or no change in residual adenosine triphosphate levels. At any given calcium concentration, the time-dependent declines in the ability of the heart to recover ventricular function was also largely independent of adenosine triphosphate levels. These studies suggest a major role of anaerobic glycolytic products (lactate, hydrogen ion, or NADH) in ischemic damage to the heart that is unrelated to loss of tissue adenine nucleotides. With zero or low flow ischemia, this effect may result in irreversible damage to the myocardium before adenine nucleotides are reduced to critically low levels. (Circ Res 55: 816-824, 1984)

show abstract

Section: Discussionmentioning

confidence: 97%

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Neely¹,

Grotyohann²

1984

Circulation Research

547

162

View full text Add to dashboard Cite

show abstract

“…Although the definitive mechanism of action for producing IMA during ischemia is unclear, the metal binding capacity of albumin for transition metals like cobalt is reduced as a consequence of the generation of reactive oxygen species that modify the metal binding capacity of the albumin moiety (31). A variety of heterogeneous ischemic conditions, including endothelial and extracellular hypoxia, acidosis, free radical injury, and sodium and calcium pump disruptions, have been associated with rapid modifications of the cobalt binding properties (47)(48)(49). Therefore, IMA should not be regarded as a specific cardiac marker, especially in patients suffering from diseases associated with enhanced oxidative stress, such as uremia (50), where the balance between prooxidant and antioxidant capacities is conventionally shifted toward an increased oxidative stress (51,52).…”

Section: Discussionmentioning

confidence: 99%

Effect of hemodialysis on traditional and innovative cardiac markers

Montagnana

Lippi

Tessitore

et al. 2008

Clinical Laboratory Analysis

View full text Add to dashboard Cite

The diagnostic approach to acute coronary syndrome (ACS) is challenging in patients with impaired renal function since most serum biomarkers are commonly increased in this clinical setting. Cardiac troponin T (cTnT), creatine kinase isoenzyme MB (CK MB), myoglobin, and ischemia modified albumin (IMA), were assayed in 45 patients prehemodialysis (pre-HD) and posthemodialysis (post-HD), and results were adjusted for hemoconcentration. The pre-HD values of serum IMA and cTnT were above the respective diagnostic thresholds (IMAo85 K units/L; cTnT o0.03 ng/mL) in six (13%) and 27 (60%) patients undergoing chronic HD, respectively. A significant (105.0 vs. 79.0 K units/L, Po0.0001) and variable (138%; 95% confidence interval [CI], 12-65%) increase of serum IMA was observed post-HD, whereas the other biomarkers significantly decreased (cTnT: 0.029 vs. 0.044 ng/mL, P 5 0.016; CK-MB:2.33 vs.2.50 mg/L, Po 0.0001; myoglobin: 128.1 vs. 148.7 mg/L, Po0.0001). Biomarkers of myocardial injury, especially cTnT and IMA, might be used in HD patients, provided that an appropriate diagnostic interpretation is guarantee, according to individual baseine value, metabolism, and time of sampling. Moreover, IMA might be reliably applied to stratify the long-term risk of these patients, but not for diagnosing an ACS during or immediately post-HD.

show abstract

“…But two experimental facts argue otherwise. First, extracellular pH drops to about neutral during ischemic pain, but not much further (14,15). Neutral pH solutions surely do not cause pain when poured onto a skinned knee, so the field has been reluctant to believe that such a modest pH change could be the source of ischemic pain.…”

Section: The Lactic Acid Paradoxesmentioning

confidence: 99%

An acid-sensing ion channel that detects ischemic pain

Naves

McCleskey

2005

Braz J Med Biol Res

View full text Add to dashboard Cite

Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (~40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.

show abstract

The time of onset and severity of acidosis in myocardial ischaemia

Cited by 235 publications

References 32 publications

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Effect of hemodialysis on traditional and innovative cardiac markers

An acid-sensing ion channel that detects ischemic pain

Contact Info

Product

Resources

About